Conditions: HER2-ve Metastatic Breast Cancer Germline BRCA1/2 Mutations Somatic BRCA1/2 Mutations
Keywords: HER2-ve metastatic breast cancer Germline BRCA1/2 mutations Somatic BRCA1/2 mutations BRCA1 BRCA2
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 256
Healthy volunteers: no

Brief summary:
This open-label, multi-centre phase IIIb study will assess the effectiveness, benefits and potential harms in the use of olaparib monotherapy treatment for patients with HER2-ve metastatic breast cancer associated with germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations.

Detailed description:
The study is a phase IIIb, multicenter, single-arm, open-label study designed to evaluate the clinical effectiveness in a real-world setting of olaparib monotherapy in patients with confirmed germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations. This study will generate additional data to support other olaparib studies, which may help inform and guide clinical practice. Physician defined the progression-free survival (PFS) for gBRCAm patients is the primary outcome measure. Based on the prevalence of gBRCA1/2 mutations, it is estimated that up to 1400 patients may require screening in order to identify 250 gBRCA mutated patients and 20 sBRCA mutated patients. Patients will be administered two olaparib 150mg tablets in morning and evening of every day after a light meal. Dose reductions may be required for olaparib treatment related toxicities. Patients should continue to receive study treatment until documented physician-defined disease progression as assessed by the investigator (gBRCA mutated patients), RECIST1.1 disease progression (sBRCA mutated patients) or unacceptable toxicity, or for as long as they do not meet any other discontinuation criteria. A positive benefit/risk profile is expected and no ethical issues are identified from exposing patients to olaparib within the planned clinical study.

Arms:
arm 1: Olaparib 150mg tablets administered orally twice daily continuously

Interventions: intervention 1: Olaparib
Intervention descriptions: intervention 1: Patients will be administered olaparib orally, twice daily at 300 mg. Two (2) 150 mg olaparib tablets should be taken at the same time each morning and evening of every day, approximately 12 hours apart.

Protocol document:
Prot_000.pdf: 
L U C Y - L y n p arz a Bre ast C a ncer Re al- W orl d Utilit y, 
Cli nic al Effecti ve ness a n d S afet y St u d y
A P h ase III b, Si n gle- ar m, O pe n-l a bel M ultice ntre St u d y of 
Ol a p ari b M o n ot her a p y i n t he Tre at me nt of H E R 2- ve 
Met ast atic Bre ast C a ncer P atie nts wit h Ger mli ne or S o m atic 
B R C A 1/ 2 M ut ati o ns
Cli nic al Tri als. g o v I de ntifier: N C T 0 3 2 8 6 8 4 2
    Ori gi n al Pr ot oc ol: 1 4 J ul 2 0 1 7  ( Versi o n 1. 0)  
A me n d me nt 1: 2 7 A pr 2 0 1 8  ( Versi o n 2. 0)  
A me n d me nt 2: 2 2 Oct  2 0 2 0 ( Versi o n 3. 0)  
A me n d me nt 3: 1 9 A pr 2 0 2 1  ( Versi o n 4. 0)














C CI
C CI
C CI
C CI


C CI
C CI
C CI
C CI
C CI
C CI




































C CI
C CI
C CI
C CI
C CI
C CI


C CI
C CI
C CI
C CI










































C CI


C CI












































C CI
C CI






C CI








































P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D












ø ¼ ¼ó Ó Ó Óó § § § § Ø Øæ ³ ³  Ë Ì Ý Æ÷





 


P P D
P P D
P P D
C CI





SAP_001.pdf: 
L U C Y - L y n p arz a Bre ast C a ncer Re al- W orl d Utilit y, 
Cli nic al Effecti ve ness a n d S afet y St u d y
A P h ase III b, Si n gle- ar m, O pe n-l a bel M ultice ntre St u d y of 
Ol a p ari b M o n ot her a p y i n t he Tre at me nt of H E R 2- ve 
Met ast atic Bre ast C a ncer P atie nts wit h Ger mli ne or S o m atic 
B R C A 1/ 2 M ut ati o ns
Cli nic al Tri als. g o v I de ntifier: N C T 0 3 2 8 6 8 4 2
 Ori gi n al S A P: 2 1 N o v  2 0 1 7  ( Versi o n 1. 0)    
A me n d me nt 1: 0 6 A u g  2 0 1 8  ( Versi o n 2. 0)  
A me n d me nt 2: 1 4 Se p 2 0 2 1 ( Versi o n 3. 0)  


  
  
  
 
  
  
 
  
  
 
 
  
  
 
St atistic al A n al ysis Pl a n 
St u d y C o de 
D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 
3. 0 
Date 
1 4- Se p- 2 0 2 1 
L U C Y - L y n p arz a Bre ast C a ncer Re al- W orl d Utilit y, Cli nic al Effe cti ve ness 
a n d S afet y St u d y  
A P h ase III b, Si n gle- ar m, O pe n-l a bel M ultice ntre St u d y of Ol a p ari b 
M o n ot her a p y i n t he Tre at me nt of H E R 2- ve Met ast atic Bre ast C a ncer 
P atie nts wit h Ger mli ne or S o m atic B R C A 1/ 2  M ut ati o ns 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2
A P h ase III b, Si n gle- ar m, O pe n-l a bel M ultice ntre St u d y of Ol a p ari b 
M o n ot her a p y i n t he Tre at me nt of H E R 2- ve Met ast atic Bre ast C a ncer 
P atie nts wit h Ger mli ne or S o m atic B R C A 1/ 2 M ut ati o ns 
St u d y St atistici a n 
 ( Pare xel)
Date 
P P D


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3
A P h ase III b, Si n gle- ar m, O pe n-l a bel M ultice ntre St u d y of Ol a p ari b 
M o n ot her a p y i n t he Tre at me nt of H E R 2- ve Met ast atic Bre ast C a ncer 
P atie nts wit h Ger mli ne or S o m atic B R C A 1/ 2 M ut ati o ns 
Gl o b al Pr o d uct St atistici a n 
 ( Astra Ze neca) 
Date 
P P D


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
4
T A B L E O F C O N T E N T S 
P A G E
TI T L E P A G E ............................................................................................................................ 1 
SI G N A T U R E O F S T U D Y S T A TI S TI CI A N ........................................................................... 2 
SI G N A T U R E O F G L O B A L P R O D U C T S T A TI S TI CI A N .................................................... 3 
T A B L E O F C O N T E N T S ......................................................................................................... 4 
LI S T O F A B B R E VI A TI O N S .................................................................................................. 7 
A M E N D M E N T HI S T O R Y .................................................................................................... 1 0 
1.  
S T U D Y D E T AI L S ................................................................................................. 1 1 
1. 1  
St u d y o bjecti ves ..................................................................................................... 1 1 
1. 2  
St u d y desi g n ........................................................................................................... 1 2 
1. 3  
N u m ber of patie nts ................................................................................................. 1 2 
2.  
A N A L Y SI S S E T S ................................................................................................. 1 3 
2. 1  
Defi niti o n of a nal ysis sets ...................................................................................... 1 3 
2. 2  
Vi olati o ns a n d de viati o ns ....................................................................................... 1 3 
3.  
P RI M A R Y A N D S E C O N D A R Y V A RI A B L E S ................................................... 1 4 
3. 1  
Calc ulati o n or deri vati o n of efficac y v aria bles ...................................................... 1 4 
3. 1. 1  
Deri vati o n of R E CI S T visit res p o nses ................................................................... 1 4 
3. 1. 1. 1 
Tar get lesi o ns ( T L) ................................................................................................ 1 4 
3. 1. 1. 2 
N T Ls a n d ne w l esi o ns ............................................................................................ 1 8 
3. 1. 1. 3 
E val uati o n of o verall visit res p o ns e ....................................................................... 2 0 
3. 1. 2  
Pr o gressi o n-free s ur vi val ....................................................................................... 2 1 
3. 1. 2. 1 
g B R C A m c o h ort .................................................................................................... 2 1 
3. 1. 2. 2 
s B R C A m c o h ort ..................................................................................................... 2 1 
3. 1. 3  
Ti me t o first s u bse q ue nt treat me nt or d eat h ( T F S T) .............................................. 2 3 
3. 1. 4  
Cli nical res p o nse rate a n d o bjecti ve res p o nse rate................................................. 2 3 
3. 1. 4. 1 
Cli nical res p o nse rate ............................................................................................. 2 3 
3. 1. 4. 2 
O bjecti ve res p o ns e rat e ( O R R) .............................................................................. 2 4 
3. 1. 5  
D urati o n of cli nical res p o nse a n d d urati o n of res p o nse ( D o R) .............................. 2 4 
3. 1. 5. 1 
D urati o n of cli nical res p o nse ................................................................................. 2 4 
3. 1. 5. 2 
D urati o n of res p o ns e .............................................................................................. 2 4 
3. 1. 6  
O verall s ur vi val ...................................................................................................... 2 5 
3. 1. 7  
Ti me t o st u d y treat me nt disc o nti n uati o n or deat h ( T D T) ...................................... 2 5 
3. 1. 8  
Ti me t o sec o n d pr o gressi o n or deat h ( P F S 2) ......................................................... 2 5 
3. 1. 9  
Ti me t o sec o n d s u bse q ue nt treat me nt or deat h ( T S S T) ......................................... 2 6 
3. 1. 9. 1 
Disease c o ntr ol rate at w ee k 2 4: ............................................................................ 2 6 
3. 2  
Calc ulati o n or deri vati o n of safet y varia bles ......................................................... 2 6 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
5
3. 2. 1  
Treat me nt e x p os ure ................................................................................................ 2 6 
3. 2. 2  
D ose i nte nsit y ......................................................................................................... 2 7 
3. 2. 3  
A d verse e ve nts ....................................................................................................... 2 8 
3. 2. 4  
La b orat or y v aria bles .............................................................................................. 2 8 
3. 3  
Calc ulati o n or deri vati o n of baseli ne varia bles ...................................................... 2 9 
3. 3. 1  
A ge ......................................................................................................................... 2 9 
3. 3. 2  
Ti me fr o m ori gi nal dia g n osis ................................................................................. 2 9 
3. 3. 3  
Pri or a n d c o nc o mita nt m e dicati o ns ........................................................................ 3 0 
3. 3. 4  
Me dical hist or y ...................................................................................................... 3 0 
3. 3. 5  
C o nc o mita nt pr oce d ures/s ur ger y ........................................................................... 3 0 
3. 4  
Ge neral c o nsi derati o ns ........................................................................................... 3 0 
3. 4. 1  
Visit wi n d o ws ........................................................................................................ 3 0 
3. 4. 2  
Defi niti o n of baseli ne ............................................................................................. 3 1 
3. 4. 3  
Missi n g data ........................................................................................................... 3 1 
4.  
A N A L Y SI S M E T H O D S ....................................................................................... 3 2 
4. 1  
Ge neral pri nci ples .................................................................................................. 3 2 
4. 2  
A nal ysis met h o d ..................................................................................................... 3 3 
4. 2. 1  
A nal ysis of t he pri mar y v aria ble ............................................................................ 3 3 
4. 2. 2  
A nal ysis of t he sec o n d ar y varia bles ....................................................................... 3 5 
4. 2. 2. 1 
O verall s ur vi val ...................................................................................................... 3 5 
4. 2. 2. 2 
Ot her ti me-t o-e v e nt e n d p oi nts ............................................................................... 3 5 
4. 2. 2. 3 
Cli nical res p o nse rate a n d o bjecti ve res p o nse rate................................................. 3 6 
4. 2. 2. 4 
Disease c o ntr ol rate ................................................................................................ 3 6 
4. 2. 3  
A nal ysis met h o ds of safet y varia bles ..................................................................... 3 6 
4. 2. 3. 1 
E x p os ure ................................................................................................................ 3 6 
4. 2. 3. 2 
A d verse e ve nts ....................................................................................................... 3 6 
4. 2. 3. 3 
Deat hs .................................................................................................................... 3 9 
4. 2. 3. 4 
La b orat or y e val uati o ns ........................................................................................... 4 0 
4. 2. 3. 5 
Electr ocar di o gra m ( E C G) ...................................................................................... 4 0 
4. 2. 3. 6 
Vital si g ns .............................................................................................................. 4 0 
4. 2. 3. 7 
Pre g na nc y test ........................................................................................................ 4 1 
4. 2. 3. 8 
O ver d ose res ults ..................................................................................................... 4 1 
4. 2. 4  
A nal ysis met h o ds of de m o gra p h y a n d b aseli ne c h aracteristics varia bles.............. 4 1 
4. 2. 4. 1 
Patie nt dis p ositi o n .................................................................................................. 4 1 
4. 2. 4. 2 
Pr ot oc ol de viati o ns ................................................................................................. 4 1 
4. 2. 4. 3 
De m o gra p hics a n d ot her baseli ne c haracteristics .................................................. 4 1 
4. 2. 4. 4 
Me dical/s ur gical hist or y ......................................................................................... 4 2 
4. 2. 4. 5 
Disease hist or y ....................................................................................................... 4 2 
4. 2. 4. 6 
C o nc o mita nt pr oce d ure/s ur ger y ............................................................................. 4 2 
4. 2. 4. 7 
C o nc o mita nt me dicati o n ........................................................................................ 4 3 
4. 2. 4. 8 
C o vi d- 1 9 data ......................................................................................................... 4 3 
4. 2. 4. 9 
Ot her e x pl orat or y a nal ys es f or de m o gr a p hics a n d baseli ne c hara cteristics ........... 4 4 
5.  
I N T E RI M A N A L Y S E S ......................................................................................... 4 4 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
6
6.  
C H A N G E S O F A N A L Y SI S F R O M P R O T O C O L ............................................... 4 6 
7.  
R E F E R E N C E S ...................................................................................................... 4 6 
8.  
A P P E N DI X ............................................................................................................ 4 6 
LI S T O F FI G U R E S 
Fi g ure 1   
E xa m ple of d ose i nte nsit y calc ulati o ns f or ola p ari b ................................. 2 7 
LI S T O F T A B L E S 
Ta ble 1   
Tar get lesi o ns visit res p o nses ................................................................... 1 5 
Ta ble 2   
E val uati o n of n o n-tar g et lesi o ns visit res p o nses ...................................... 1 9 
Ta ble 3  
O verall visit res p o ns e ............................................................................... 2 0 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
7
LI S T O F A B B R E VI A TI O N S 
A b bre vi ati o n or 
s peci al ter m 
E x pl a n ati o n 
A E 
A d verse e ve nt 
A E SI 
A d verse e ve nt of s pecial i nterest 
AJ C C 
A merica n j oi nt c o m mittee o n ca ncer 
A L T 
Ala ni ne a mi n otra nsferase 
A M L 
Ac ute m yel oi d le u kae mia 
A S T 
As partate a mi n otra nsferase 
A T C 
A nat o mical t hera pe utic c he mical 
B R C A 1, B R C A 2, 
B R C A 1/ 2  
Breast ca ncer s usce pti bilit y ge nes 
CI 
C o nfi de nce i nter val 
c m 
Ce nti metres 
C N S 
Ce ntral ner v o us s yste m 
C O VI D- 1 9 
C or o na vir us disease 2 0 1 9 
C R 
C o m plete res p o nse 
C R R 
Cli nical res p o nse rate 
C S P 
Cli nical st u d y pr ot oc ol 
C S R 
Cli nical st u d y re p ort 
C T 
C o m p ute d t o m o gra p h y 
C T C 
C o m m o n t o xicit y criteria 
C T C A E 
C o m m o n ter mi n ol o g y criteria f or a d verse e ve nt 
D C O 
Data c ut- off 
D C R 
Disease c o ntr ol rate 
D o C R 
D urati o n of cli nical res p o nse 
D o R 
D urati o n of res p o nse 
d. p. 
Deci mal place 
E C G 
Electr ocar di o gra m 
E C O G 
Easter n C o o perati ve O nc ol o g y Gr o u p 
e C R F 
Electr o nic case re p ort f or m 
E R 
Estr o ge n rece pt or 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
8
A b bre vi ati o n or 
s peci al ter m 
E x pl a n ati o n 
F A S 
F ull a nal ysis set 
g B R C A m 
Ger mli ne B R C A 1/ 2 m utati o n 
H E R 2- ve 
H u ma n e pi der mal gr o wt h fact or rece pt or 2 ne gati ve 
I N R 
I nter nati o nal n or malise d rati o 
K M 
Ka pla n- Mei er 
L D 
L o n gest dia meter 
M D S 
M yel o d ys plastic s y n dr o me 
Me d D R A 
Me dical Dicti o nar y f or Re g ulat or y Acti vities 
m m 
Milli metre 
N CI 
Nati o nal Ca ncer I nstit ute 
N A 
N ot a p plica ble 
N E 
N ot e val ua ble 
N T L 
N o n-tar get lesi o ns 
O R R 
O bjecti ve res p o nse rate 
O S 
O verall s ur vi val 
P D 
Pr o gressi ve disease 
P E T 
P ositr o n e missi o n t o m o gra p h y 
P F S 
Pr o gressi o n free s ur vi val 
P F S 2 
Ti me t o sec o n d pr o gressi o n or deat h 
PI D 
Perce nta ge i nte n de d d ose 
P R 
Partial res p o nse 
P R 
Pr o gester o ne rece pt or 
P T 
Preferre d ter m 
R DI 
Relati ve d ose i nte nsit y 
R E CI S T 
Res p o nse E val uati o n Criteria I n S oli d T u m o urs 
S A E 
Seri o us a d verse e ve nt  
S A P 
Statistical a nal ysis pla n 
s B R C A m 
S o matic B R C A 1/ 2 m utati o n 
S D 
Sta ble disease 
S O C 
S yste m or ga n class 
T D T 
Ti me t o st u d y treat me nt disc o nti n uati o n or deat h 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
9
A b bre vi ati o n or 
s peci al ter m 
E x pl a n ati o n 
T E A E 
Treat me nt-e mer ge nt a d verse e ve nt 
T F S T 
Ti me t o first s u bse q ue nt treat me nt or deat h 
T L 
Tar get lesi o ns 
U L N 
U p per li mit of n or mal ra n ge 
T S S T 
Ti me t o sec o n d s u bse q ue nt treat me nt or deat h 
W H O 
W orl d Healt h Or ga nizati o n 








St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
1 3
2.  
A N A L Y SI S S E T S 
2. 1  
Defi niti o n of a n al ysis sets 
Data fr o m t he g er mli ne a n d s o matic B R C A m utate d patie nt c o h orts will be prese nte d 
se parat el y a n d c o m bi ne d, u nless ot her wise st at e d. 
F ull A n al ysis Set 
T he F ull A nal ysis Set ( F A S) will i ncl u de all patie nts w h o recei v e at least o ne d ose of ola p ari b. 
T he F A S will be use d f or all efficac y a n d s afet y a nal yses. 
All P atie nts Set 
All patie nts scree n e d will be i ncl u de d i n t his set, w hic h will be use d f or listi n gs of baseli ne 
data a n d f or a s mall n u m ber of s u m mar y ta bl es (e. g. patie nt dis p ositi o n). 
2. 2  
Vi ol ati o ns a n d de vi ati o ns 
A list of all cate g ories of pr ot oc ol de viati o ns wit h a classificati o n of eac h pr ot oc ol de viati o n as 
“ n ot i m p orta nt” (“ mi n or”) or “i m p orta nt” (“ maj or ”) is i ncl u de d i n t he Pr ot oc ol De viati o ns 
S pecificati o ns d oc u me nt.  Pr ot oc ol de viati o ns will be i de ntifie d eit her pr o gra m maticall y base d 
o n t he electr o nic case re p ort f or m (e C R F) data or base d o n t he me dical re vi e w of data listi n gs 
or base d o n m o nit ori n g n otes.  Pr ot oc ol de viati o ns will be re vie we d re g ularl y a n d als o 
classifie d as r elate d t o C or o na vir us dise as e 2 0 1 9 ( C O VI D- 1 9) or n ot rel ate d t o C O VI D- 1 9.   
A s u bset of t he maj or pr ot oc ol de viati o ns will be c o nsi dere d as i m p orta nt. 
T he f oll o wi n g ge ner al cate g ories will be c o nsi der e d i m p orta nt pr ot oc ol de viati o ns.  T hese will 
be liste d a n d s u m marise d a n d disc usse d i n t he cli nical st u d y re p ort ( C S R) as a p pr o priate: 
Patie nts e ntere d b ut w h o di d n ot recei ve st u d y treat me nt ( De viati o n 1). 
Patie nts w h o de viate fr o m ke y e ntr y criteria per C S P ( De viati o n 2):  
o
I n cl usi o n criteria 3, 4, 5, 6 
o
E xcl usi o n criteria 4, 5, 1 3 
Baseli ne R E CI S T sca n > 4 2 da ys bef or e first d ose of st u d y treat me nt ( D e viati o n 3) 
(s B R C A m c o h ort o nl y).  
N o baseli ne R E CI S T 1. 1 ass ess me nt o n or bef ore date of first d ose of st u d y treat me nt 
( De viati o n 4) (s B R C A m c o h ort o nl y). 
Recei ve d pr o hi bite d c o nc o mita nt me dicati o ns (i ncl u di n g ot her a nti-ca n cer a ge nts) 
( De viati o n 5). C S P secti o n 7. 7 descri bes me dicati o ns t hat are det aile d as bei n g 
‘e xcl u de d’ fr o m per mitte d use d uri n g t he st u d y. T his will be use d as a g ui di n g 
pri nci ple; t he cate g orisati o n of t hese as i m p orta nt de viati o ns is n ot a ut o matic a n d will 
de pe n d o n a me di cal re vi e w of me dicati o n listi n gs. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
1 4
T he fi nal classificati o n of de viati o ns will be ma de pri or t o data base l o c k or data fr eeze. 
Decisi o ns ma de will be d oc u me nte d a n d a p pr o ve d b y Astra Ze neca pri or t o data base l oc k. 
3. 
P RI M A R Y A N D S E C O N D A R Y V A RI A B L E S 
3. 1  
C alc ul ati o n or deri v ati o n of effic ac y v ari a bles 
I n t his real w orl d st u d y t u m o ur e val uati o n is per i nstit uti o nal sta n dar d of care f or t he 
g B R C A m patie nts. T he date of t u m o ur ass ess me nt, met h o d of e val uati o n (r a di ol o gical 
res p o nse e v al uati o n criteria i n s oli d t u m o urs [ R E CI S T], r a di ol o gical n o n- R E CI S T, 
cli nical/s y m pt o matic), ra di ol o gical assess me nt ( c o m p ut e d t o m o gra p h y [ C T], ma g neti c 
res o na nce i ma gi n g [ M RI], x-ra y, ultras o u n d, b o ne sca n, p ositr o n e missi o n t o m o gra p h y [ P E T] 
sca n, sci nti gra p h y) a n d t he i n vesti gat ors o pi ni o n of t he patie nt stat us (res p o n di n g, sta ble, 
pr o gressi n g) is ca pt ure d i n t he T u m o ur assess me nt e C R F pa ge. R E CI S T ass ess me nt of t u m o ur 
res p o nse is n ot ma n date d or ca pt ur e d a n d t here is n o re q uire me nt t o c o nfir m res p o nse f or 
t hese patie nts.  
F or t he s B R C A m patie nts, t he R E CI S T t u m o ur res p o ns e data rec or d e d i n t he T u m o ur 
e val uati o n e C R F pa g es b ase d o n t he i n vesti gat or’s re vie w of t h e i ma gi n g sca ns will be use d t o 
deter mi ne eac h patie nt’s visit res p o nses acc or di n g t o R E CI S T versi o n 1. 1. N o ce ntr al re vie w 
will be perf or me d. 
3. 1. 1  
Deri v ati o n of R E CI S T visit res p o nses 
F or t he s B R C A m patie nt c o h ort, baseli ne r a di ol o gical t u m o ur assess me nts p erf or me d wit hi n 6 
wee ks of first d ose of ola pari b ar e ac ce pta ble.  T u m o ur assess me nts ar e t he n perf or me d e ver y 
4 wee ks u p t o wee k 1 2, t he n e ver y 6 wee ks u p t o wee k 4 8 a n d t h e n e ver y 1 2 wee ks t her eaft er. 
I n Fra nce a n d Ger ma n y, t u m o ur assess me nts will occ ur e v er y 4 w ee ks u p t o wee k 4 8, a n d 
t he n e ver y 1 2 wee ks t hereafter. 
Baseli ne val ues r ec or d e d after first d ose of ola pari b s h o ul d n ot be use d as t he baseli ne 
assess me nt; alt h o u g h s uc h ass ess me nts ca n b e use d i n t he calc ulati o n of pr o gressi ve diseas e 
( P D).   
At eac h visit, patie nts will be pr o gra m maticall y assi g ne d a n o verall visit res p o nse of c o m plete 
res p o nse ( C R), partial r es p o nse ( P R), st a ble diseas e ( S D) or P D de p e n di n g o n t he stat us of 
t heir disease c o m p are d wit h baseli ne a n d pre vi o us assess me nts.  If a p atie nt has ha d a t u m o ur 
assess me nt, w hic h ca n n ot be e val uate d, t he n t he p atie nt will be assi g ne d a visit res p o nse of 
n ot e val ua ble ( N E) ( u nless t here is e vi de nce of pr o gressi o n i n w hic h cas e t he res p o nse will be 
assi g ne d as P D). 
3. 1. 1. 1 
T ar get lesi o ns ( T L) 
Meas ura ble dis ease is defi ne d as ha vi n g at least o ne meas ura ble lesi o n, n ot pre vi o usl y 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
1 5
re peat e d meas ur e me nts. A patie nt ca n h a ve a m a xi m u m of fi ve meas ura bl e lesi o ns rec or d e d at 
baseli ne wit h a ma xi m u m of t w o lesi o ns per or ga n (re pr ese ntati ve of all lesi o ns i n v ol ve d a n d 
s uita ble f or acc urate re p eate d meas ur e me nt) a n d t hese are referre d t o as tar get lesi o ns ( T Ls). If 
m ore t ha n o ne bas eli ne s ca n is rec or de d t he n m eas ure me nts fr o m t he o ne t hat is cl osest a n d 
pri or t o baseli ne will be use d t o defi ne t he b aseli ne s u m of T Ls. It ma y be t he case t h at, o n 
occasi o n, t he lar gest lesi o n d oes n ot le n d itself t o re pr o d uci ble m eas ur e me nt. I n w hi c h 
circ u msta nce t he ne xt lar gest lesi o n, w hic h ca n b e meas ure d r e pr o d u ci bl y, s h o ul d be selecte d. 
All ot her lesi o ns ( or sites of disease) n ot rec or de d as T Ls s h o ul d be i de ntifie d as n o n-tar g et 
lesi o ns ( N T Ls) at bas eli ne. Me as ur e me nts ar e n ot re q uire d f or t hese lesi o ns, b ut t heir stat us 
s h o ul d be f oll o we d at s u bse q ue nt visits. 
Ta ble 1 pr o vi des t he d efi niti o ns of t he criteria use d t o deter mi ne o bjecti ve t u m o ur visit 
res p o nse f or T Ls. 
T a ble 1   
T ar get lesi o ns visit res p o nses 
C R  
Disa p pear a nc e of all T Ls si nce baseli ne.  A n y p at h ol o gical l y m p h n o des 
selecte d as T Ls m ust ha ve a re d u cti o n i n s h ort a xis t o < 1 0 m m. 
P R  
At least a 3 0 % decre ase i n t he s u m of t he dia meters of T L, ta ki n g as refer e n ce 
t he baseli ne s u m of dia m eters as l o n g as criteria f or P D are n ot m et. 
P D  
At least a 2 0 % i ncr eas e i n t he s u m of dia meters of T Ls a n d a n a bs ol ute i ncrease 
starte d i ncl u di n g t he baseli ne s u m of dia meters. 
S D  
Neit her s uffi cie nt s hri n ka ge t o q ualif y f or P R n or s ufficie nt i ncr ease t o q u alif y 
f or P D. 
N E  
O nl y rele va nt if a n y of t h e T Ls wer e n ot assesse d or N E or ha d a lesi o n 
i nter ve nti o n at t his visit.  N ote:  If t he s u m of dia m eters meets t he P D crit eri a, 
P D o verri des N E as a T L res p o ns e. 
N ot 
a p plica ble 
( N A) 
N o T Ls are rec or de d at baseli ne. 
R o u n di n g of T L d at a 
F or calc ulati o n of P D a n d P R, f or T Ls t he perce nta ge c h a n ges fr o m b aseli n e a n d pre vi o us 
mi ni m u m s h o ul d be r o u n de d t o o ne deci mal place ( d. p.) bef ore assi g ni n g a T L res p o nse. F or 
e xa m ple, 1 9. 9 5 % s h o ul d be r o u n de d t o 2 0. 0 % b ut 1 9. 9 4 % s h o ul d be r o u n de d t o 1 9. 9 %. 
Missi n g T L d at a 
F or a visit t o be e v al ua bl e t he n all T L meas ure me nts s h o ul d be rec or d e d. H o we ver, a visit 
res p o nse of P D s h o ul d still be assi g ne d if a n y of t h e f oll o wi n g occ urre d: 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
1 6
A ne w lesi o n is rec or de d 
A N T L visit res p o nse of P D is rec or de d 
T he s u m of T Ls is s uffici e ntl y i ncreas e d t o r es ult i n a 2 0 % i ncr ease, a n d a n a bs ol ute 
N ote: t he na dir ca n o nl y be ta ke n fr o m assess me nts w here all t he T Ls h a d a L D rec or de d. 
If t here is at least o ne T L meas ure me nt missi n g a n d a visit res p o nse of P D ca n n ot be assi g ne d, 
t he visit res p o nse is N E. 
L y m p h n o des 
F or l y m p h n o des, if t he size re d u ces t o < 1 0 m m t he n t h ese are c o nsi dere d n o n- pat h ol o gical. 
H o we ver, a size will still be gi ve n a n d t his size s h o ul d still be use d t o deter mi ne t he T L visit 
res p o nse as n or mal. I n t h e s pe cial c ase w h ere all l y m p h n o des are < 1 0 m m a n d all ot her T Ls 
are 0 m m t he n alt h o u g h t he s u m ma y be > 0 m m t he calc ul ati o n of T L res p o nse s h o ul d be 
o ver- writte n as a C R. 
T L visit res p o nses s u bse q ue nt t o C R 
C R, P D or N E ca n o nl y f oll o w a C R. If a C R has occ urre d, t he n t he f oll o wi n g r ules at t he 
s u bse q ue nt visits m ust be a p plie d: 
Ste p 1: If all lesi o ns meet t he C R criteria (i.e. 0 m m or < 1 0 m m f or l y m p h n o des) t he n 
res p o nse will be set t o C R irr es p ecti ve of w het her t he criteria f or P D of T L is als o met 
i.e. if a l y m p h n o de L D i ncreas es b y 2 0 % b ut re mai ns < 1 0 m m. 
Ste p 2: If s o me lesi o n meas ure m e nts are missi n g b ut all ot her lesi o ns meet t he C R 
criteria (i. e. 0 m m or < 1 0 m m f or l y m p h n o des) t he n res p o nse will be set t o N E 
irres pecti ve of w het h er, w he n refer e nci n g t he s u m of T L dia meters, t he criteria f or P D 
are als o met. 
Ste p 3: If n ot all lesi o ns meet t he C R criteria a n d t he s u m of lesi o ns meets t he criteria 
f or P D t he n res p o ns e will be set t o P D. 
Ste p 4: If after ste ps 1 – 3 a res p o nse ca n still n ot be deter mi ne d t he res p o nse will be 
set t o re mai n as C R. 
T L t o o bi g t o me as u re 
If a T L b ec o mes t o o bi g t o meas ure t his s h o ul d be i n dicate d i n t he data bas e a n d a size (‘ x’) 
a b o ve w hic h it ca n n ot be acc ur atel y meas ure d s h o ul d be rec or de d. If usi n g a val ue of x i n t he 
calc ulati o n of T L res p o nse w o ul d n ot gi ve a n o verall visit res p o nse of P D, t he n t his will be 
fla g ge d a n d re vie w e d pri or t o data base l o c k or dat a freeze. It is e x pecte d t hat a visit res p o nse 
of P D will re mai n i n t he vast maj orit y of cases. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
1 7
T L t o o s m all t o me as ure
If a T L b ec o mes t o o s mall t o meas ure, t he n t his will be i n dicate d as s uc h o n t he e C R F a n d a 
val ue of 5 m m will be e ntere d i nt o t he data b ase a n d use d i n T L calc ulati o ns. H o we ver, a 
s maller val ue ma y b e use d if t he ra di ol o gist has n ot i n dicate d ‘t o o s mall t o meas ure’ o n t h e 
e C R F a n d has e ntere d a s maller val ue t hat ca n be r elia bl y meas ure d. If a T L res p o nse of P D 
res ults, t he n t his will be re vie we d pri or t o data bas e l oc k or data freez e. 
Irr a di ate d lesi o ns/lesi o n i nter ve nti o n 
Pre vi o usl y irra diate d lesi o ns (i.e. lesi o n irra diate d pri or t o e ntr y i nt o t he st u d y) s h o ul d be 
rec or d e d as N T Ls a n d s h o ul d n ot f or m part of t he T L assess me nt. 
A n y T L (i ncl u di n g l y m p h n o des), w hic h has h a d i nter ve nti o n d uri n g t he st u d y (f or e x a m ple, 
irra diati o n / palliati ve s ur ger y / e m b olisati o n), s h o ul d be ha n dle d i n t he f oll o wi n g wa y a n d 
o nce a lesi o n has h a d i nter ve nti o n t he n it s h o ul d be treate d as ha vi n g i nter v e nti o n f or t he 
re mai n der of t he st u d y n oti n g t hat a n i nter ve nti o n will m ost li kel y s hri n k t he si ze of t u m o urs: 
Ste p 1: t he dia meters of t he T Ls (i ncl u di n g t he lesi o ns t hat ha ve ha d i nter v e nti o n) will 
be s u m me d a n d t he calc ulati o n will be perf or me d i n t he us ual ma n ner. If t he visit 
res p o nse is P D, t his will re mai n as a v ali d res p o ns e cate g or y. 
Ste p 2: If t here w as n o e vi de nce of pr o gressi o n after st e p 1, treat t he lesi o n dia meter 
meas ure me nts t he n s cale u p as descri be d i n t he ‘ Scali n g’ secti o n bel o w. If t he scali n g 
res ults i n a visit res p o nse of P D t he n t he patie nt w o ul d be assi g ne d a T L res p o nse of 
P D. 
of t he T Ls ha ve missi n g meas ur e me nts), t h e scale d s u m of dia meters c alc ulate d i n ste p 
2 s h o ul d be use d, a n d P R or S D t he n assi g ne d as t he visit res p o nse. Patie nts wit h 
i nter ve nti o n are e val ua bl e f or C R as l o n g as all n o n-i nter ve ne d l esi o ns are 0 m m ( or 
< 1 0 m m f or l y m p h n o des) a n d t he lesi o ns t hat ha ve bee n s u bject t o i nter ve nti o n ha ve a 
val ue of 0 m m ( or < 1 0 m m f or l y m p h n o des) rec or de d. If scali n g u p is n ot a p pr o priate 
d ue t o t o o fe w n o n- missi n g meas ure me nts t he n t h e visit res p o nse will be set as N E. 
At s u bse q ue nt visits, t he a b o ve st e ps will be re p eate d t o deter mi ne t he T L a n d o verall visit 
res p o nse. W h e n calc ulati n g t he pre vi o us mi ni m u m, lesi o ns wit h i nter ve nti o n s h o ul d be treate d 
as missi n g a n d scale d u p (as per st e p 2 a b o ve).
Sc ali n g ( a p plic a ble o nl y f or irr a di ate d lesi o ns/lesi o n i nter ve nti o n) 
If > 1/ 3 of T L me as ure m e nts are missi n g ( beca use of i nter ve nti o n) t he n t he T L res p o nse will 
be N E, u nless t he s u m of dia meters of n o n- missi n g T L w o ul d res ult i n P D (i.e. if usi n g a val ue 
of 0 m m f or missi n g lesi o ns, t he s u m of dia meters has still i ncrease d b y 2 0 % or m ore 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
1 8
scale d u p ( b ase d o n t he sizes at t he na dir visit t o gi ve a n esti mate d s u m of dia meters a n d t his 
will be use d i n calc ulati o ns; t his is e q ui vale nt t o c o m pari n g t he visit s u m of dia meters of t h e 
n o n- missi n g lesi o ns t o t he na dir s u m of dia meters e xcl u di n g t he lesi o ns wit h missi n g 
meas ure me nts. 
E x a m ple of sc ali n g 
Lesi o n 5 is missi n g at t he f oll o w- u p visit. 
T he s u m of lesi o ns 1- 4 dia meters at t he f oll o w- u p visit is 2 6 ce nti metres (c m). T he s u m of t he 
c orres p o n di n g lesi o n dia meters at t he na dir visit is 2 6. 8 c m. T he s u m of all lesi o n dia meters at 
t he na dir visit is 2 9. 3 c m. 
Scale u p as f oll o ws t o gi ve a n esti mat e d T L s u m of 2 8. 4 c m: 
( 2 6 / 2 6. 8) × 2 9. 3 = 2 8. 4 c m 
C R will n ot be all o we d as a T L res p o nse f or visits w here t here is missi n g data. O nl y P R, S D 
or P D ( or N E) c o ul d be assi g ne d as t he T L visit res p o ns e i n t hese cas es. H o we ver, f or visits 
i ncl u de d w he n defi ni n g t he na dir val ue f or t he assess me nt of pr o gr essi o n. 
Lesi o ns t h at s plit i n t w o 
If a T L s plits i n t w o, t he n t he L Ds of t he s plit lesi o ns s h o ul d be s u m me d a n d re p orte d as t he 
L D f or t he lesi o n t hat s plit. 
Lesi o ns t h at mer ge 
If t w o T Ls mer g e, t he n t he L D of t he mer ge d lesi o n s h o ul d be rec or de d f or o ne of t he T L 
sizes a n d t he ot her T L size s h o ul d be r ec or d e d as 0 m m. 
C h a n ge i n m et h o d of assess me nt of T Ls 
C T sca n a n d M RI are t he o nl y met h o ds of assess me nt t hat ca n be us e d wit hi n t his trial.  If a 
c ha n ge i n met h o d of assess me nt occ urs bet wee n C T a n d M RI, t his will be c o nsi dere d 
acce pta ble a n d n o a dj ust me nt wit hi n t he pr o gra m mi n g is nee de d. 
3. 1. 1. 2  
N T Ls a n d ne w lesi o ns 
At eac h visit, t he i n vesti gat or s h o ul d rec or d a n o verall ass ess me nt of t he N T L res p o nse. T his 
secti o n pr o vi des t he defi niti o ns of t he criteria use d t o deter mi ne a n d rec or d o verall res p o ns e 
f or N T L at t he i n v esti gati o nal site at eac h visit. 
N T L res p o nse will be deri ve d base d o n t he i n vesti gat or’s o ver all assess me nt of N T Ls as 
f oll o ws: 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
1 9
T a ble 2   
E v al u ati o n of n o n-t ar get lesi o ns visit res p o nses 
C R 
Disa p pear a nce of all N T Ls prese nt at bas eli ne wit h all l y m p h n o des n o n-
pat h ol o gical i n size ( < 1 0 m m s h ort a xis). 
P D 
U ne q ui v ocal pr o gressi o n of e xisti n g N T Ls.  U ne q ui v ocal pr o gressi o n 
ma y be d ue t o a n i m p orta nt pr o gressi o n i n o ne lesi o n o nl y or i n se veral 
lesi o ns.  I n all cases t he pr o gressi o n M U S T be cli nicall y si g nifica nt f or 
t he p h ysicia n t o c o nsi der c ha n gi n g ( or st o p pi n g) t h era p y. 
N o n C R/ N o n P D 
Persiste nce of o n e or m ore N T L wit h n o e vi de n ce of pr o gressi o n. 
N E 
O nl y rele va nt w h e n o ne or s o me of t he N T Ls w er e n ot assesse d a n d, i n 
t he i n vesti gat or's o pi ni o n, t he y are n ot a bl e t o pr o vi de a n e val u a ble 
o verall N T L ass ess me nt at t his visit. 
N ote:  F or p atie nts wit h o ut T Ls at baseli ne, t his is rele va nt if a n y of t he 
N T Ls were n ot assesse d at t his visit a n d t he pr o gressi o n crit eria h a ve n ot 
bee n met. 
N A 
O nl y rele va nt if t here are n o N T Ls at baseli ne. 
T o ac hie ve ‘ u ne q ui v ocal pr o gressi o n’ o n t he b asis of N T Ls, t here m ust be a n o verall le vel of 
s u bsta ntial w orse ni n g i n n o n-tar get diseas e s uc h t hat, e ve n i n pres e nce of S D or P R i n T Ls, 
t he o verall t u m o ur b ur de n has i ncre ase d s uffi cie ntl y t o merit dis c o nti n uati o n of t hera p y.  A 
m o dest i ncrease i n t he si ze of o ne or m ore N T Ls is us uall y n ot s ufficie nt t o q ualif y f or 
u ne q ui v ocal pr o gressi o n stat us. 
Ne w lesi o ns 
Details of a n y ne w lesi o ns will als o be rec or d e d wit h t he date of assess me nt. T he prese n ce of 
o ne or m ore n e w lesi o ns is ass ess e d as pr o gr essi o n. 
A lesi o n i de ntifie d at a f oll o w- u p assess me nt i n a n a nat o mical l ocati o n t hat was n ot sca n ne d at 
baseli ne is c o nsi dere d a ne w lesi o n a n d will i n dicate disease pr o gressi o n. 
T he fi n di n g of a ne w lesi o n s h o ul d be u ne q ui v ocal: i.e. n ot attri b uta ble t o differe n ces i n 
sca n ni n g tec h ni q ue, c ha n ge i n i ma gi n g m o dalit y or fi n di n gs t h o u g ht t o re prese nt s o met hi n g 
ot her t ha n t u m o ur. 
Ne w lesi o ns will be i de ntifie d via a Yes/ N o tic k b o x. T he a bse n ce a n d pres e nce of n e w lesi o ns 
at eac h visit s h o ul d be list e d al o n gsi de t he T L a n d N T L visit res p o nses. 
A ne w lesi o n i n dicates pr o gressi o n s o t he o ver all visit r es p o nse will be P D irres pecti ve of t he 
T L a n d N T L res p o nse. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 0
If t he q uesti o n ‘ A n y n e w lesi o ns si nce baseli ne’ h as n ot bee n a ns w er e d wit h Yes or N o a n d 
t he ne w lesi o n details ar e bla n k t his is n ot e vi de nce t hat n o ne w lesi o ns are prese nt b ut s h o ul d 
n ot o vertl y affect t he deri vati o n. 
S y m pt o matic pr o gressi o n is n ot a descri pt or f or pr o gressi o n of N T Ls: it is a reas o n f or 
st o p pi n g st u d y t hera p y a n d will n ot be i ncl u de d i n a n y assess me nt of N T Ls. 
Patie nts wit h ‘s y m pt o matic pr o gressi o n’ r e q uiri n g disc o nti n uati o n of ola pari b wit h o ut 
o bjecti ve e vi de nce of dis ease pr o gressi o n at t hat ti me s h o ul d c o nti n ue t o u n der g o t u m o ur 
assess me nts w here p ossi ble u ntil o bjecti ve dise ase pr o gressi o n is o bser v e d. 
3. 1. 1. 3 
E v al u ati o n of o ver all visit res p o nse 
T he o verall visit res p o nse will be deri ve d usi n g t he al g orit h m s h o w n i n Ta ble 3. 
T a ble 3  
O ver all visit res p o nse 
T ar get Lesi o ns  
N o n- T ar get 
Lesi o ns 
Ne w Lesi o ns  
O ver all Res p o nse 
C R 
C R or N A  
N o ( or N E)  
C R 
C R 
N o n C R/ N o n P D or 
N E 
N o ( or N E)  
P R 
P R 
N o n P D or N E or 
N A 
N o ( or N E)  
P R 
S D  
N o n P D or N E or 
N A 
N o ( or N E)  
S D 
P D 
A n y 
A n y 
P D 
A n y 
P D 
A n y 
P D 
A n y 
A n y 
Yes 
P D 
N E 
N o n P D or N E or 
N A 
N o ( or N E)  
N E 
N A 
C R 
N o ( or N E)  
C R 
N A 
N o n C R/ N o n P D   
N o ( or N E)  
S D 
N A 
N E 
N o ( or N E)  
N E 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 1
3. 1. 2 
Pr o gressi o n-f ree s ur vi v al 
3. 1. 2. 1 
g B R C A m c o h ort 
I n g B R C A m patie nts, dise ase pr o gressi o n is base d o n i n vesti gat or assess me nt, i.e. ra di ol o gical 
( R E CI S T, n o n- R E CI S T) pr o gressi o n, or cli nical/s y m pt o matic pr o gressi o n, as l o n g as 
pr o gressi o n ca n b e d oc u me nte d.  
P F S is defi ne d as t he ti me ( da ys) fr o m t he date of t he first d ose of ola pari b u ntil t he date of 
disease pr o gressi o n or deat h ( b y a n y ca use i n t he a bse nce of pr o gr essi o n) re gar dless of 
w het her t he p atie nt wit h dra ws fr o m t hera p y or recei ves a n ot her a nti-ca n cer t hera p y pri or t o 
pr o gressi o n (i.e. d ate of P F S e ve nt or ce ns ori n g – date of first d ose of ola p ari b + 1).  
T he e C R Fs will ca pt ure eac h ti me a patie nt is assesse d f or pr o gressi o n re g ar dless of t he 
o utc o me of t he assess me nt. Patie nts w h o ha ve n ot pr o gresse d or die d at t he ti me of a nal ysis 
will be ce ns ore d at t he ti me of t he latest date of assess me nt fr o m t heir last e val ua ble 
pr o gressi o n assess me nt. If t he patie nt has n o e v al u a ble pr o gr essi o n assess me nts, t he y will be 
ce ns ore d at st u d y da y 1.  
T he P F S ti me f or g B R C A m patie nts will be deri v e d base d o n t he t u m o ur assess me nt date as 
rec or d e d i n t he T u m o ur assess me nt e C R F pa ge, n ot visit dates.  
3. 1. 2. 2 
s B R C A m c o h ort 
I n s B R C A m patie nts, dise ase pr o gressi o n is deter mi ne d b y R E CI S T versi o n 1. 1 ( Eise n ha uer 
E A, 2 0 0 9).  
P F S is defi ne d as t he ti me ( da ys) fr o m t he date of t he first d ose of ola pari b u ntil t he date of 
o bjecti ve disease pr o gressi o n or deat h ( b y a n y ca use i n t he a bse nce of pr o gressi o n) re g ar dless 
of w het her t h e patie nt wit h dra ws fr o m t hera p y or recei v es a n ot her a nti-ca ncer t her a p y pri or t o 
pr o gressi o n (i.e. d ate of P F S e ve nt or ce ns ori n g – date of first d ose of ola p ari b + 1). 
Patie nts w h o ha ve n ot pr o gresse d or die d at t he ti me of a nal ysis will be ce ns ore d at t he ti me of 
t he latest date of ass ess me nt fr o m t heir last e v al ua ble R E CI S T assess me nt. 
H o we ver, if t he patie nt pr o gresses or di es after t w o or m or e miss e d visits, t he patie nt will be 
ce ns ore d at t he ti me of t h e latest e val ua bl e p ost- baseli ne R E CI S T assess me nt pri or t o t he 
misse d visits ( or ce ns or e d at ola pari b start dat e i n case of n o e val ua bl e p ost- baseli ne sca n pri or 
t o t he misse d visits).  T he all o we d ga p b et wee n t he last pre vi o us e val u a ble p ost- baseli ne 
R E CI S T assess me nt ( or ola pari b start date i n case of n o pre vi o us e v al ua ble p ost- baseli ne 
assess me nt) a n d t he pr o gressi o n or deat h, f or w hic h t he pr o gressi o n/ deat h will still be c o u nte d 
as a n e ve nt, will be d efi n e d as: 
All o we d ga p  = 2 *(sc he d ul e d ti me bet wee n sca ns) + all o we d visit wi n d o w 
= 2 *( 4 we e ks) + 1 wee k 
= 9 wee ks ( 6 3 da ys) 
if t here is n o e val u a ble p ost- baseli ne sca n pri or t o t he pr o gressi o n or d eat h. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 2
All o we d ga p  = 2 *(sc he d ul e d ti me bet wee n sca ns + all o w e d visit wi n d o w) 
= 2 *(sc he d ul e d ti me bet wee n sca ns + 1 w ee k)  
= 1 0 wee ks ( 7 0 da ys) f or patie nts i n t he e ver y- 4- w ee ks sc he d ul e 
= 1 2 wee ks ( 8 4 da ys) f or patie nts c ha n gi n g fr o m e ver y 4 t o e ver y 6 wee ks 
= 1 4 wee ks ( 9 8 da ys) f or patie nts i n t he e ver y- 6- w ee ks sc he d ul e 
= 2 0 wee ks ( 1 4 0 da ys) f or patie nts c ha n gi n g fr o m e ver y 6 t o e v er y 1 2 wee ks 
= 2 6 wee ks ( 1 8 2 da ys) f or patie nts i n t he e ver y- 1 2- wee ks s c he d ul e 
if t here is a n e v al ua ble p ost- baseli ne sca n pri or t o t he pr o gressi o n or d eat h. 
T he first r ule all o ws o n e misse d visit directl y after t he ola pari b start dat e a n d t he ne xt visit o ne 
wee k later t ha n pla n ne d t o c o nsi der t he ± 1 wee k visit wi n d o w.  T he sec o n d r ule all o ws o ne 
missi n g visit a n d c o nsi ders t hat t he pre vi o us sca n ma y be 1 wee k earlier t h a n pla n ne d a n d t h e 
pr o gressi o n visit 1 wee k later t ha n pla n ne d, si n ce t he all o we d visit wi n d o w is ± 1 wee k.  
F or a last pre vi o us e val u a ble sca n at We e k 4 ± 1 t he patie nt is still i n t he e ver y- 4- w ee ks 
sc he d ule, f or a last pre vi o us e val ua ble sc a n at Wee k 8 ± 1 t he patie nt c ha n g es fr o m e ver y- 4-
wee ks t o e ver y- 6- wee ks, f or a last pr e vi o us e val ua ble sca n fr o m Wee k 1 2 ± 1 t o Wee k 3 6 ± 1 t he 
patie nt is still i n t he e ver y- 6- wee ks sc he d ule, f or a last pre vi o us e val u a ble sca n at Wee k 4 2 ± 1 
t he patie nt c ha n ges fr o m e ver y- 6- wee ks t o e ver y- 1 2- wee ks, a n d f or a last pr e vi o us e val ua ble 
sca n at Wee k 4 8 ± 1 or lat er t he patie nt is i n t he e v er y- 1 2- wee ks s c he d ule.  T he mi d p oi nts of 
t he i nter vals fr o m Wee k 4 t o Wee k 8, Wee k 8 t o Wee k 1 2, Wee k 3 6 t o Wee k 4 2 a n d fr o m 
Wee k 4 2 t o Wee k 4 8 will be use d t o se parate t he t hree peri o ds, a n d t he all o we d ga ps bet wee n 
t he last pre vi o us e val ua bl e p ost- baseli ne R E CI S T assess m e nt ( or ola p ari b start date i n cas e of 
n o pre vi o us e val ua bl e p ost- baseli ne ass ess me nt) a n d t he pr o gressi o n or d eat h will be defi ne d 
as: 
All c o u ntries e xcl u di n g Fra nce/ G er ma n y: 
All o we d ga p =  
9 wee ks ( 6 3 d a ys)   
if n o e val ua ble p ost- b aseli ne sca n pri or t o t he pr o gressi o n/ deat h 
1 0 wee ks ( 7 0 d a ys)  if last pre vi o us e val ua bl e p ost- baseli ne sca n < Wee k 6 ( Da y 4 2) 
 < We e k 1 0 ( D a y 7 0) 
 < We e k 3 9 ( D a y 2 7 3) 
 < We e k 4 5 ( D a y 3 1 5) 
Si nce Fra nce a n d Ger ma n y ha ve differe nt visit sc he d ules (e v er y 4 wee ks f or t he first 4 8 wee ks 
a n d t he n e ver y 1 2 wee ks) t he defi niti o n of t he all o we d ga p c h a n ges as f oll o ws: 
Fra n ce/ Ger ma n y 
All o we d ga p =  
9 wee ks ( 6 3 d a ys)   
if n o e val ua ble p ost- b aseli ne sca n pri or t o t he pr o gressi o n/ deat h 
1 0 wee ks ( 7 0 d a ys)  if last pre vi o us e val ua bl e p ost- baseli ne sca n < Wee k 4 2 ( Da y 2 9 4) 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 3
 < We e k 4 6 ( D a y 3 2 2) 
Misse d visits are o nl y rele va nt i m me diatel y pri or t o a pr o gressi o n or d eat h.  If a patie nt misse d 
t w o or m ore visits a n d has a S D, P R or C R i m me diatel y t hereafter, t he n t h e miss e d visits ca n 
be i g n ore d f or t he deri v ati o n of P F S. 
T he P F S f or s B R C A m patie nts will al wa ys be deri ve d base d o n sca n/assess me nt dates n ot 
visit dates. 
R E CI S T assess me nts/sca ns c o ntri b uti n g t o war ds a partic ular visit ma y be p erf or me d o n 
differe nt d ates.  T he f oll o wi n g r ules will be a p plie d: 
Date of pr o gressi o n will be deter mi ne d b ase d o n t he earliest of t h e dates of t he 
c o m p o ne nt t hat tri g gere d t he pr o gressi o n. 
W he n ce ns ori n g a patie nt f or P F S, t he patie nt will be ce ns or e d at t he latest of t he dates 
c o ntri b uti n g t o a partic ular o ver all visit assess me nt. 
3. 1. 3 
Ti m e t o first s u bse q ue nt tre at m e nt or de at h ( T F S T) 
T F S T is defi ne d as t he ti me fr o m t he date of t he first d ose of ola pari b t o t he earliest of t he d ate 
of deat h or c o m me nce m e nt of first s u bse q ue nt a nti-ca ncer treat me nt as r ec or de d i n t he Ti me 
t o s u bse q ue nt ca ncer t her a p y e C R F pa g e (i.e. dat e of deat h or c o m me nce m e nt of first 
s u bse q ue nt a nti-ca n cer treat me nt - date of first d ose of ola pari b + 1). A n y patie nt n ot k n o w n t o 
ha ve ha d a first s u bse q ue nt a nti-ca ncer t her a p y will be ce ns or e d at t he last date after t he 
disc o nti n uati o n of ola pari b t hat t he patie nt was k n o w n n ot t o ha ve recei ve d a first s u bse q ue nt 
a nti-ca ncer t hera p y ( o btai ne d fr o m t he Ti me t o s u bse q ue nt ca n cer t h era p y e C R F pa ge). If a 
patie nt ter mi nates t he st u d y f or a re as o n ot her t ha n deat h bef ore first s u bs e q ue nt t hera p y, t he y 
will be ce ns ore d at t he earliest of t heir last k n o w n t o be ali ve a n d ter mi nati o n dates. 
If at least o ne s u bs e q ue nt t hera p y is rec or de d, b ut t he start date of t h e first s u bse q ue nt t hera p y 
is missi n g, t he n T F S T will be ce ns ore d at t he last date after t he disc o nti n uati o n of ola pari b t he 
patie nt was k n o w n t o ha v e n ot starte d a s u bse q u e nt t hera p y. 
3. 1. 4  
Cli nic al res p o nse r ate a n d o bjecti ve res p o nse r ate 
3. 1. 4. 1  
Cli nic al res p o nse r ate 
Res p o nse i n g B R C A m patie nts is base d o n t he i n vesti gat or’s assess me nt. T he C R R is defi ne d 
as t he pr o p orti o n of patie nts wit h at least o ne visit i n w hic h t he i n vesti gat or assesse d t he 
patie nt as res p o n di n g. Data o btai ne d u p u ntil pr o gressi o n, or last e val ua ble assess me nt i n t he 
a bse nce of pr o gr essi o n, will be i ncl u de d i n t he assess me nt of C R R. H o we ver, a n y res p o nses, 
w hic h occ urre d after a f urt her a nti-c a ncer t hera p y was recei ve d (as rec or d e d i n t he P ost st u d y 
dr u g disc o nti n uati o n ca n cer t hera p y e C R F p a ge), will n ot be i ncl u de d i n t he n u merat or f or t he 
C R R calc ulati o n. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 4
3. 1. 4. 2  
O bjecti ve res p o nse r ate ( O R R) 
Res p o nse i n s B R C A m pati e nts m ust be base d o n R E CI S T 1. 1. O R R is defi ne d as t he 
perce nt a ge of p atie nts wit h a c o nfir me d i n vesti gat or-assesse d res p o nse of C R or P R a n d will 
base d o n a s u bset of all treate d patie nts wit h meas ura ble dis eas e at bas eli ne per t he site 
i n vesti gat or. A c o nfir me d res p o ns e of C R/ P R mea ns t hat a res p o ns e of C R/ P R is rec or de d at 1 
visit a n d c o nfir me d b y re peat i ma gi n g n ot less t ha n 4 wee ks after t he visit w he n t he res p o ns e 
was first o bser v e d wit h n o e vi de nce of pr o gr essi o n bet wee n t he i nitial a n d C R/ P R 
c o nfir mati o n visit.  Data o btai ne d u p u ntil pr o gressi o n, or last e val ua ble ass ess me nt i n t he 
a bse nce of pr o gr essi o n, will be i ncl u de d i n t he assess me nt of O R R. Patie nts w h o dis c o nti n ue 
ola pari b wit h o ut pr o gressi o n, recei ve a s u bse q ue nt a nti-ca ncer t hera p y ( n ot e t hat f or t his 
a nal ysis ra di ot hera p y is n ot c o nsi dere d a s u bs e q ue nt a nti-ca ncer t hera p y) a n d t he n res p o n d 
will n ot be i ncl u de d as res p o n ders (i.e. b ot h visits c o ntri b uti n g t o a res p o ns e m ust be pri or t o 
s u bse q ue nt a nti-ca n cer t hera p y f or t he patie nt t o b e c o nsi der e d as a res p o n d er). 
I n t he cas e w her e a p atie nt has t w o n o n-c o nsec uti ve visit res p o nses of P R, t he n, as l o n g as t he 
ti me bet wee n t he t w o visits of P R is gr eater t ha n 4 wee ks a n d t h ere is n o P D bet wee n t h e P R 
visits, t he patie nt will be defi ne d as a res p o n d er. Si milarl y, if a patie nt has visit res p o nses of 
C R, N E, C R, t he n, as l o n g as t he ti me bet wee n t h e t w o visits of C R is gr eater t ha n 4 wee ks, 
t he n a best res p o ns e of C R will be assi g ne d. 
3. 1. 5  
D ur ati o n of cli nic al res p o nse a n d d ur ati o n of res p o nse ( D o R) 
3. 1. 5. 1  
D ur ati o n of cli nic al res p o nse 
F or patie nts wit h a cli nical res p o nse i n t he g B R C A m c o h ort, D o C R is defi ne d as t he ti me 
fr o m t he date of first res p o nse, u ntil t he date of d o c u me nte d pr o gr essi o n or deat h (i.e. dat e of 
P F S e ve nt or ce ns ori n g – date of first res p o nse + 1). T he e n d of res p o nse s h o ul d c oi nci de wit h 
t he date of pr o gressi o n or deat h use d f or t he P F S e n d p oi nt. T he ti me of t he i nitial res p o nse 
will be base d o n t he t u m o ur assess me nt ca pt ure d i n t he e C R F.  
If a patie nt d o es n ot pr o gress f oll o wi n g a res p o nse, t he y will be ce ns ore d at t he P F S ce ns ori n g 
date.  
3. 1. 5. 2  
D ur ati o n of res p o nse 
F or patie nts i n t he s B R C A m c o h ort, D o R is defi n e d as t he ti me fr o m t he d ate of first 
d oc u me nte d res p o ns e ( w hic h is s u bse q ue ntl y c o nfir me d) u ntil date of d oc u me nte d pr o gressi o n 
or deat h i n t he a bs e nce of disease pr o gressi o n (i.e. date of P F S e v e nt or ce ns ori n g – date of 
first res p o ns e + 1). T he e n d of res p o nse s h o ul d c oi nci de wit h t he date of pr o gressi o n or deat h 
use d f or t he P F S e n d p oi nt. T he ti me of t he i nitial res p o nse will be defi ne d as t he latest of t he 
dates c o ntri b uti n g t o war ds t he first visit t hat was C R or P R t hat was s u bse q ue ntl y c o nfir me d. 
If a patie nt d o es n ot pr o gress f oll o wi n g a res p o nse, t he y will be ce ns ore d at t he P F S ce ns ori n g 
date.  


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 5
3. 1. 6  
O ver all s ur vi v al 
S ur vi val calls will be ma de i n t he wee k f oll o wi n g t he date of dat a c ut- off ( D C O) f or t he 
a nal ysis, a n d if patie nts ar e c o nfir m e d t o be ali ve or if t he deat h d ate is p ost t he D C O date 
t hese patie nts will be ce ns or e d at t he dat e of D C O.  T he st at us of o n g oi n g, wit h dra w n (fr o m 
t he st u d y) a n d “l ost t o f oll o w- u p” patie nts at t he ti me of t he fi nal O S a n al ysis s h o ul d be 
o btai ne d b y t he site pers o n nel b y c hec ki n g t he p atie nt’s n otes, h os pital rec or ds, c o ntacti n g t he 
patie nt’s ge ner al practiti o ner a n d c h ec ki n g p u blicl y-a vaila ble d eat h re gistri es. I n t he e v e nt t hat 
t he patie nt has acti vel y wit h dra w n c o nse nt t o t he pr ocessi n g of t heir pers o n al data, t he vital 
stat us of t he patie nt ca n b e o btai ne d b y site pers o n nel fr o m p u blicl y a vail a ble res o urces w here 
it is p ossi ble t o d o s o u n der a p plica bl e l ocal la ws. 
O S is defi ne d as t he ti me fr o m t he date of t he first d ose of ola pari b t o t he date of deat h fr o m 
a n y ca use (i.e. dat e of deat h – date of first d ose of ola pari b + 1). Patie nts w h o are n ot k n o w n 
t o ha ve die d at t he ti me of t he a nal ysis will be ce ns ore d at t he last date t h e y were k n o w n t o be 
ali ve. 
If a patie nt is k n o w n t o h a ve die d w h ere o nl y a p artial deat h date is a v aila ble t he n t he date of 
deat h will be i m p ute d as t he latest of t he last date k n o w n t o be ali ve + 1 fr o m t he data base a n d 
t he deat h date usi n g t he a vaila ble i nf or mati o n pr o vi de d:- 
a.  
F or Missi n g da y o nl y – usi n g t he 1st of t he m o nt h  
b.  
F or Missi n g da y a n d M o nt h – usi n g t he 1st of Ja n uar y 
c.  
T his i ncl u des deat hs w here n o partial d eat h date was rec or de d, b ut t he a v aila ble 
s ur vi val data all o ws t o c o ncl u de t hat t he deat h date w as wit hi n a m o nt h or wit hi n a year, i.e. 
last date k n o w n t o be ali ve a n d first c o ntact date w he n t he patie nt is re p orte d as dea d are 
wit hi n t he sa me m o nt h or sa me year. 
If t here is e vi de nce of deat h b ut t he date is e ntirel y missi n g, it will be treat e d as missi n g, i.e. 
ce ns ore d at t he last k n o w n ali ve date. 
3. 1. 7 
Ti m e t o st u d y tre at m e nt disc o nti n u ati o n or de at h ( T D T) 
T D T is defi ne d as t he ti me fr o m t he date of t he first d ose ola pari b t o t he earliest of t he date of 
deat h or disc o nti n uati o n of ola pari b. Patie nts w h o are ali ve a n d are still recei vi n g ola pari b will 
be ce ns or e d at t he last date t heir treat me nt w as rec or de d as bei n g a d mi nist ere d. 
3. 1. 8 
Ti m e t o sec o n d pr o gressi o n or de at h ( P F S 2) 
P F S 2 is defi ne d as t he ti me fr o m t he date of t he first d ose ola pari b t o t he earliest of t he date of 
deat h or t he pr o gressi o n e ve nt s u bse q ue nt t o t hat use d f or t h e pri mar y vari a ble P F S as 
rec or d e d i n t he T u m o ur assess me nt f or sec o n d pr o gressi o n e C R F pa g e. Patie nts ali ve a n d f or 
w h o m a sec o n d dise ase pr o gressi o n has n ot bee n o bser ve d will be ce ns ore d at t he last date 
t he y were k n o w n t o be ali ve. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 6
If a se c o n d pr o gressi o n was re c or de d, b ut t he pr o gressi o n date is missi n g, t he n P F S 2 will be 
ce ns ore d at t he date of t he last e val ua ble t u m o ur assess me nt f or a se c o n d pr o gressi o n ( P F S 2 
e C R F pa ge) w here a n o n- pr o gressi o n w as assesse d.  
3. 1. 9 
Ti m e t o sec o n d s u bse q ue nt tre at m e nt or de at h ( T S S T) 
T S S T is defi ne d as t he ti me fr o m t he date of t he first d ose ola pari b t o t he earliest of t he date of 
deat h or c o m me n ce me nt of t he sec o n d s u bs e q u e nt a nti-ca ncer tr eat me nt as rec or d e d i n t he 
Ti me t o s u bse q ue nt ca ncer t her a p y e C R F pa g e. Patie nts w h o are ali ve a n d ha ve n ot bee n 
rec or d e d as ta ki n g t w o s u bse q ue nt a nti-ca ncer treat me nts will be ce ns ore d at t he last date t heir 
treat me nt stat us was r ec or de d. If a patie nt ter mi nat es t he st u d y f or a reas o n ot her t ha n deat h 
bef ore s ec o n d s u bse q u e nt t hera p y, t he y will be ce ns ore d at t he earliest of t heir last k n o w n t o 
be ali ve a n d ter mi nati o n dates. 
If at least t w o s u bse q u e nt t hera pies are rec or d e d, a n d b ot h t he start date of t he first s u bse q ue nt 
t hera p y a n d t he st art date of t he sec o n d s u bse q u e nt t her a p y ar e missi n g, t he n T F S T a n d T S S T 
will be ce ns ore d o n t h e last date t he patie nt w as k n o w n t o ha ve n ot st art e d a s u bse q ue nt 
t hera p y. 
If at least t w o s u bse q u e nt t hera pies are rec or d e d, t he start date of t h e first s u bse q ue nt t hera p y 
is k n o w n, b ut t he start date of t he sec o n d s u bs e q ue nt t hera p y is missi n g, t he n T S S T will be 
ce ns ore d o n t h e latest of ( 1) last date t he p atie nt was k n o w n t o ha ve n ot starte d a sec o n d 
s u bse q ue nt t hera p y a n d ( 2) o ne da y after t he st art date of t he first s u bs e q u e nt t hera p y. 
3. 1. 9. 1  
Dise ase c o ntr ol r ate at wee k 2 4: 
A m o n g t he s u bset of patie nts wit h br ai n metastases at baseli ne, D C R is defi ne d as n o e vi de n ce 
of pr o gressi o n ( C R, P R or S D) at or pri or t o wee k 2 4 as assesse d b y a n M RI or C T sca n. 
3. 2  
C alc ul ati o n or deri v ati o n of s afet y v ari a bles 
3. 2. 1 
Tre at m e nt e x p os ure 
Ola pari b is ta ke n d ail y. He nce, t otal (i nte n d e d) e x p os ure ti me ( m o nt hs) of ola pari b will be 
calc ulate d as f oll o ws: 
T otal ( or i nte n de d) e x p os ure ( m o nt hs) = (earliest of (last d ose date w here d ose > 0 m g, 
deat h date, D C O d ate) – first d ose date + 1) / 3 0. 4 3 7 5 
Act ual e x p os ur e ( m o nt hs) of ola pari b will be calc ulate d as f oll o ws: 
Act ual e x p os ur e = t otal e x p os ure – t otal d urati o n of d ose i nterr u pti o ns i n m o nt hs 
(i ncl u di n g da ys w here d ose = 0 m g), w here t otal e x p os ure will be cal c ulate d as a b o ve a n d 
a d ose i nterr u pti o n is defi ne d as a n y le n gt h of ti me w here t he p atie nt has n ot ta ke n a n y of 
t he pla n ne d d ose. T h e act ual e x p os ure calc ulati o n ma kes n o a dj ust me nt f or a n y d ose 
re d ucti o ns t hat ma y ha v e occ urre d. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 7
F or patie nts still o n ola pari b at t he ti me of t he i nteri m a nal ysis, t he D C O date will be use d t o 
calc ulate e x p os ure. 
3. 2. 2  
D ose i nte nsit y 
Relati ve d ose i nte nsit y ( R DI) is t he perce nta ge of t he act ual d ose d eli vere d relati ve t o t he 
i nte n de d d ose t hr o u g h t o treat me nt disc o nti n uati o n. R DI will be d efi ne d as f oll o ws: 
w here d is t he act ual c u m ulati ve d ose deli ver e d u p t o t he earlier of pr o gr essi o n ( or a ce ns ori n g 
e ve nt, see s ecti o n 3. 1. 2) or t he act ual last d a y of d osi n g a n d D is t he i nte n de d c u m ulati ve d ose 
u p t o t he earlier of pr o gressi o n ( or a ce ns ori n g e v e nt) or t he act ual last da y of d osi n g. 
Perce nta g e i nte n de d d ose ( PI D) is t he per ce nta g e of t he act ual d os e deli ver e d relati ve t o t he 
i nte n de d d ose t hr o u g h t o pr o gressi o n a n d will be d efi ne d as f oll o w: 
w here d is t he act ual c u m ulati ve d ose deli ver e d u p t o pr o gressi o n ( or a ce ns ori n g e ve nt) a n d D 
is t he i nte n de d c u m ulati ve d ose u p t o pr o gr essi o n ( or a ce ns ori n g e v e nt).  D is t he t otal d ose 
t hat w o ul d be deli vere d, if t here w ere n o m o difi cati o n t o d ose or sc he d ule. 
Fi g ure 1 E x a m ple of d ose i nte nsit y c alc ul ati o ns f or ol a p ari b 
I n t his e x a m ple, patie nts 1 - 5 pr o gress e d or were ce ns ore d o n st u d y d a y 1 5.  All fi ve patie nts 
recei v e d less treat me nt t ha n i nte n de d d ue t o: 
•  
Misse d/f or g otte n d oses ( Patie nt 1) 
•  
D ose re d u cti o n a n d earl y st o p pi n g ( Patie nt 2) 
•  
D ose i nterr u pti o n ( Patie nt 3) 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 8
•  
Pr o gressi o n w hilst o n d ose i nterr u pti o n ( Patie nt 4)  
•  
Earl y st o p pi n g ( Patie nt 5) 
P atie nt 1 :  
R DI = PI D = [( 1 2 * 3 0 0 m g * 2) + ( 2 * 3 0 0 m g)] / ( 1 4 * 3 0 0 m g * 2) = 9 3 % 
P atie nt 2 :  
R DI = [( 7 * 3 0 0 m g * 2) + ( 4 * 2 5 0 m g * 2)] / ( 1 1 * 3 0 0 m g * 2) = 9 4 % 
PI D = [( 7 * 3 0 0 m g * 2) + ( 4 * 2 5 0 m g * 2)] / ( 1 4 * 3 0 0 m g * 2) = 7 4 % 
P atie nt 3:   
R DI = PI D = ( 9 * 3 0 0 m g * 2) / ( 1 4 * 3 0 0 m g * 2) = 6 4 % 
P atie nt 4:   
R DI = ( 1 2 * 3 0 0 m g * 2) / ( 1 2 * 3 0 0 m g * 2) = 1 0 0 % 
PI D = ( 1 2 * 3 0 0 m g * 2) / ( 1 4 * 3 0 0 m g * 2) = 8 6 %  
P atie nt 5:   
R DI = [( 5 * 3 0 0 m g * 2) + ( 1 * 3 0 0 m g)] / ( 6 * 3 0 0 m g * 2) = 9 2 % 
PI D = [( 5 * 3 0 0 m g * 2) + ( 1 * 3 0 0 m g)] / ( 1 4 * 3 0 0 m g * 2) = 3 9 % 
3. 2. 3  
A d verse e v e nts 
A d verse e ve nts ( A Es) ( b ot h i n ter ms of t he Me dic al Dicti o nar y f or R e g ulat or y Acti vities 
[ Me d D R A] preferre d t er ms [ P T] a n d Nati o nal Ca ncer I nstit ute [ N CI] C o m m o n Ter mi n ol o g y 
Criteria f or A d v erse E v e nt [ C T C A E] gra de) will be liste d i n di vi d uall y b y patie nt. 
A treat me nt-e mer ge nt A E ( T E A E) is a n A E wit h a n o nset date or a pre-e xisti n g A E w orse ni n g 
f oll o wi n g t he first d ose of ola pari b t hr o u g h t o 3 0 da ys after t h e l ast d ose of ola pari b. O nl y 
T E A Es will be i ncl u de d i n t he A E s u m mar y ta bles.  A n y A E occ urri n g bef or e ola pari b (i.e. 
bef ore t h e a d mi nistrati o n of t he first d ose o n st u d y da y 1) will be i ncl u de d i n t he A E listi n gs, 
b ut will n ot be i ncl u de d i n t he s u m mar y ta bles ( u nless ot her wise state d). T h ese will be 
referre d t o as ‘ pre-treat me nt’. H o we v er, a n y A E o cc urri n g b ef or e t he a d mi nistrati o n of t he 
first d ose of ola pari b o n st u d y da y 1 t hat i ncreas es i n se verit y after t he first d ose will be 
re gar d e d as treat me nt e m er ge nt a n d t h us will be i n cl u de d i n t he maj orit y of s u m mar y ta bles. 
F or patie nt le v el s u m maries, if m ore t ha n o ne A E is c o de d t o t he sa me P T f or t he sa me 
patie nt, t he patie nt will be c o u nte d o nl y o nce i n s u m mar y ta bles usi n g t he m ost seri o us 
gra di n g o n ca us al relati o ns hi p t o ola pari b. 
3. 2. 4 
L a b or at or y v ari a bles 
La b orat or y d ata will be c ollecte d t hr o u g h o ut t he st u d y, fr o m scree ni n g t o t he f oll o w- u p visits 
as per t he st u d y pla n des cri be d i n t he C S P. T hese i ncl u de bl o o d sa m ples f or deter mi nati o n of 
hae mat ol o g y. F or t h e defi niti o n of baseli ne a n d t he deri vati o n of p ost- b aseli ne visit val ues 
c o nsi deri n g visit wi n d o w a n d h o w t o ha n dle m ulti ple rec or ds, d eri vati o n r ules descri be d i n 
secti o n 3. 4 will be use d. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
2 9
C ha n ge fr o m bas eli ne i n hae mat ol o g y varia bl es will be calc ulate d f or eac h visit o n treat me nt 
a n d u p t o 3 0 da ys after last d ose of ola pari b. C o m m o n t o xicit y criteria ( C T C) gra des will be 
defi ne d at eac h visit acc or di n g t o t he C T C gra de criteria usi n g l ocal or pr oj ect ra n g es as 
re q uire d, after c o n versi o n of t he la b orat or y res ult t o c orres p o n di n g pr oje ct- wi de preferre d 
u nits.  
A bs ol ute val ues will be c o m pare d t o t he pr oject refere n ce ra n ge a n d classifi e d as l o w ( bel o w 
ra n ge), n or mal ( wit hi n ra n ge or o n li mits of ra n ge) a n d hi g h (a b o ve ra n ge). 
T he ma xi m u m ( or mi ni m u m) o n-treat me nt val u e ( de pe n di n g o n t he directi o n of a n a d verse 
effect) will be defi ne d f or eac h l a b orat or y p ar a meter as t he ma xi m u m ( or mi ni m u m) p ost- d ose 
val ue at a n y ti me. 
L ocal refer e nce ra n g es will be use d f or t he pri mar y i nter pretati o n of la b orat or y data at t he 
l ocal la b orat or y. Pr oject refer e nce ra n g es will be use d t hr o u g h o ut f or re p orti n g p ur p oses. T he 
de n o mi nat or use d i n la b orat or y s u m maries of C T C gra des will o nl y i ncl u de e val ua bl e 
patie nts, i n ot her w or ds t h ose w h o ha d s uffi cie nt data t o ha ve t h e p ossi bilit y of a n 
a b n or malit y. 
F or e x a m ple: 
If a C T C criteri o n i n v ol v es a c ha n g e fr o m b aseli n e, e val ua bl e patie nts w o ul d ha ve b ot h a 
baseli ne a n d at least o ne p ost- d ose val ue rec or d e d. 
If a C T C criteri o n d o es n ot c o nsi der c ha n g es fr o m baseli ne, t o be e v al ua ble t he patie nt 
nee ds o nl y t o ha ve o ne p ost d ose- val ue r ec or d e d. 
3. 3  
C alc ul ati o n or deri v ati o n of b aseli ne v ari a bles 
3. 3. 1  
A ge 
If a ge is missi n g b ut date of birt h is pr ese nt, a ge will be calc ulate d as f oll o ws ( wit h o ut 
r o u n di n g): 
A ge ( years) = (st u d y da y 1 – date of birt h) / 3 6 5. 2 5 
T his will be deter mi ne d fr o m t he date of birt h ( birt h date i n t he De m o gr a p hics e C R F pa g e) 
a n d baseli ne visit (‘ visit 2’ i n t he Date of visit e C R F pa ge). If t he d a y of birt h is missi n g, t he 
first da y of t he m o nt h will be i m p ute d a n d if da y a n d m o nt h are missi n g Ja n uar y 1st will be 
i m p ute d.  
3. 3. 2 
Ti m e fr o m ori gi n al di a g n osis 
Ti me fr o m ori gi nal dia g n osis ( m o nt hs) will be calc ulate d as f oll o ws: 
Ti me fr o m ori gi nal dia g n osis ( m o nt hs) = (st u d y da y 1 - ori gi nal dia g n osis date + 1) / 3 0. 4 3 7 5 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 0
If t he ori gi nal dia g n osis da y is missi n g, t he first da y of t he m o nt h will be i m p ute d, a n d if da y 
a n d m o nt h are missi n g Ja n uar y 1st will be i m p ute d. 
3. 3. 3 
Pri or a n d c o nc o mit a nt m e dic ati o ns 
T he W orl d H ealt h Or ga nisati o n ( W H O) Dr u g B 3 dicti o nar y will be use d f or c o nc o mita nt 
me dicati o n c o di n g. 
A n y me dicati o ns ta ke n b y t he patie nt pri or t o or d uri n g scree ni n g wit h a st o p date pri or t o t he 
first d ose of ola pari b will be c o nsi dere d pri or me di cati o n.  
A n y me dicati o n ta ke n b y t he patie nt at a n y ti me after t he date of t he first d ose (i ncl u di n g t he 
date of t he first d ose) of ola pari b u p t o 3 0 da ys aft er last d os e will be c o nsi dere d c o n c o mita nt 
me dicati o n.  A n y me dicati o n t hat starte d pri or t o t he first d ose of ola p ari b a n d e n de d aft er t he 
first d ose or is o n g oi n g will be c o nsi dere d as b ot h pri or a n d c o n c o mita nt me dicati o n. 
F or t he p ur p os e of i ncl usi o n i n pri or or c o nc o mita nt me diati o n s u m maries, i nc o m pl ete 
me dicati o n start a n d st o p dates will be i m p ute d as detaile d i n secti o n 3. 4. 3. 
3. 3. 4  
Me dic al hist or y 
Rele va nt me dical hist or y ( past a n d c urre nt) a n d rele va nt s ur gical hist or y will be c o de d usi n g 
t he latest versi o n of Me d D R A. 
3. 3. 5  
C o nc o mit a nt pr oce d ures/s ur ger y 
C o nc o mita nt pr oce d ures/s ur ger y will be c o d e d usi n g t he latest versi o n of Me d D R A. A n y 
pr oce d ure occ urri n g at a n y ti me after t he d ate of t he first d ose (i ncl u di n g t he date of t he first 
d ose) of ola pari b u p t o 3 0 da ys after l ast d ose will be c o nsi der e d c o nc o mita nt.   
3. 4  
Ge ner al c o nsi der ati o ns  
3. 4. 1  
Visit wi n d o ws 
Ti me wi n d o ws will nee d defi ni n g f or a n y prese ntati o ns t hat s u m marise val u es b y visit. T he 
f oll o wi n g c o n ve nti o ns s h o ul d als o a p pl y f or all visits e xce pt f or wit h dr a wal, safet y f oll o w a n d 
l o n g-ter m f oll o w u p visits, w hic h will be prese nte d se parat el y: 
T he ti me wi n d o ws s h o ul d be e x ha usti ve s o t hat d ata rec or de d at a n y ti me p oi nt has t he 
p ote ntial t o be s u m marise d. I ncl usi o n wit hi n t he ti me wi n d o w s h o ul d be base d o n t he 
act ual date a n d n ot t he i nte n de d date of t h e visit. 
All data fr o m visits as descri be d i n t he visit sc he d ule i n t he C S P a n d a n y ot her visits 
s h o ul d ha ve t he p ote ntial t o be i ncl u de d i n t he s u m maries. 
T he wi n d o w f or t h e visits f oll o wi n g baseli ne will be c o nstr ucte d i n s u c h a wa y t h at t he 
u p per li mit of t he i nter val falls half wa y bet w ee n t he t w o visits (t he l o wer li mit of t he first 
p ost- baseli ne visit will be st u d y da y 2). If a n e v e n n u m ber of da ys e xists bet wee n t w o 
c o nsec uti ve visits t he n t he u p per li mit will be ta ke n as t he mi d p oi nt val ue mi n us o ne da y. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 1
F or s u m maries s h o wi n g t he ma xi m u m or mi ni m u m val ues, t he ma xi m u m/ mi ni m u m val ue 
rec or d e d o n treat me nt will be use d (re g ar dless of w here it falls i n a n i nter v al). 
Listi n gs s h o ul d dis pla y all val ues c o ntri b uti n g t o a ti m e p oi nt f or a patie nt. 
F or visit- base d s u m mari es, if t here is m ore t ha n o n e val ue per patie nt wit hi n a ti me 
wi n d o w t he n t he val ue cl osest t o t he pla n ne d st u d y da y s h o ul d be s u m marise d, or t he 
earlier i n t he e ve nt t he val ues are e q ui dista nt fr o m t he pla n ne d st u d y da y.  
3. 4. 2  
Defi niti o n of b aseli ne 
Baseli ne will be defi ne d as t he last n o n- missi n g meas ure m e nt pri or t o d osi n g wit h ola pari b. 
Assess me nts o n t he da y of t he first d ose w h ere n eit her ti me n or a n o mi nal pre- d ose i n dicat or 
are ca pt ure d will be c o nsi dere d pri or t o t he first d ose if s u c h pr oce d ur es are re q uire d b y t he  
C S P t o be c o n d ucte d bef ore t he first d ose. W here safet y data are s u m marize d o ver ti me, st u d y 
da y will be calc ul ate d i n relati o n t o date of first d ose of ola pari b. 
3. 4. 3  
Missi n g d at a 
Missi n g safet y data will ge nerall y n ot be i m p ute d. H o we ver, saf et y assess me nt val ues of t he 
f or m of “ < x” (i.e., b el o w t he l o wer li mit of q ua ntificati o n) or > x (i. e., a b o ve t he u p per li mit of 
q ua ntificati o n) will be i m p ute d as “ x” i n t he calc ul ati o n of s u m mar y st atistics b ut dis pla ye d as 
“ < x” or “ > x ” i n t he listi n gs. 
F or missi n g me dicati o n a n d A E start dates, t he f oll o wi n g will be a p plie d: 
If year is missi n g ( or c o m pletel y missi n g), t he n i m p ute wit h t he first st u d y dr u g d ose date 
u nless t he A E e n d date is pri or t o t he first st u d y dr u g d ose date, i n w hic h case t he A E start 
date is i m p ute d wit h 0 1-Ja n of t he sa me y ear as t h e A E e n d dat e. 
If year is prese nt a n d m o nt hs a n d da y ar e missi n g; or year a n d da y are pres e nt a n d m o nt h 
is missi n g, i m p ute as Ja n uar y 1st. 
If year a n d m o nt h ar e prese nt a n d da y is missi n g, i m p ute da y as first da y of t he m o nt h. 
F or missi n g me dicati o ns a n d A E e n d d ates, t he f oll o wi n g will be a p plie d: 
If year is missi n g ( or c o m pletel y missi n g), d o n ot i m p ute. 
If year is prese nt a n d m o nt h a n d da y ar e missi n g; or year a n d da y are prese nt a n d m o nt h is 
missi n g, i m p ute as Dece m ber 3 1st. 
If year a n d m o nt h ar e prese nt a n d da y is missi n g, i m p ute da y as last da y of t he m o nt h. 
W he n t he patie nt h as die d i n t he sa me m o nt h/ year of partial st o p date, use date of deat h. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 2
F or me dicati o ns, a c o nser vati ve a p pr o ac h will be f oll o we d a n d will be ass u me d t o be 
c o nc o mita nt u nless t he e n d date is bef ore t he first d ose of ola pari b. If t he st art a n d e n d d ates 
are b ot h missi n g it is c o nsi dere d c o n c o mita nt.  
I n a d diti o n, f or A Es, if f or a partial start date, t he A E start date c o ul d ( w he n als o c o nsi deri n g 
t he A E e n d date) p ote ntiall y be o n t he first d ose of ola pari b date, t he A E start date will be 
i m p ute d wit h t he first d ose of ola pari b d ate t o ass u me a “ w orst case ” sce n ari o; e. g. A E fr o m 
U N K-J u n- 2 0 1 7 t o 2 3-J ul- 2 0 1 7 wit h t he first d ose of ola pari b dat e 2 1-J u n- 2 0 1 7, t he n t he A E 
start date will be i m p ute d t o 2 1-J u n- 2 0 1 7. 
4.  
A N A L Y SI S M E T H O D S 
4. 1  
Ge ner al pri nci ples 
N o h y p ot hesis testi n g is pla n ne d f or t his si n gle ar m st u d y. 
T he f oll o wi n g ge ner al pri nci ples will be f oll o we d t hr o u g h o ut t he st u d y: 
C o nti n u o us varia bles will be s u m marise d b y t he n u m ber of o bser v ati o ns, mea n, 
sta n dar d de viati o n, me di a n, mi ni m u m, ma xi m u m a n d first a n d t hir d q uartil es w here 
re q uire d. Cate g orical v aria bles will be s u m marise d b y fre q ue n c y c o u nts a n d 
perce nt a ges f or eac h cate g or y. A cate g or y “ Missi n g” will be a d de d o nl y if n ee de d. 
U nless ot her wise state d, perce nt a ges will be c al c ulate d o ut of t he p o p ul ati o n t otal. 
T he mi ni m u m a n d ma xi m u m will be re p orte d t o t he sa me n u m ber of d. p. as t he ra w 
data rec or de d i n t he d ata base. T he mea n, me dia n, first a n d t hir d q uartile will be 
re p orte d t o o ne m or e d. p., a n d t he sta n dar d d e viati o n will be re p orte d t o t w o m ore d. p., 
t ha n t he ra w d ata rec or d e d i n t he data base. 
Perce nta g es will be pres e nte d t o o ne d. p.. 
S A S ® versi o n 9. 3 will be use d f or all a nal yses. 
F or ti me i nter val a nal yses i n m o nt hs, d urati o n i n m o nt hs will be calc ulate d as t otal 
d urati o n i n da ys / 3 0. 4 3 7 5. 
St u d y da y 1 is defi ne d as t he date of first d ose of ola pari b. F or visits ( or e v e nts) t hat 
occ ur o n or after first d os e, st u d y da y is defi ne d as ( date of visit [e v e nt] - date of first 
d ose of ola pari b + 1). F or visits ( or e ve nts) t hat occ ur pri or t o first d ose, st u d y da y is 
defi ne d as ( d ate of visit [e ve nt] - d ate of first d ose of ola pari b). T here is n o st u d y 
da y 0. 
I n all s u m maries c ha n g e fr o m baseli ne varia bles will be calc ulate d as t he p ost-
treat me nt val ue - baseli n e val ue. T he p erce nta ge c ha n ge fr o m b aseli ne will be 
calc ulate d as [( p ost- b aseli ne val ue - bas eli ne val ue) / baseli ne val ue] × 1 0 0. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 3
4. 2  
A n al ysis met h o d 
4. 2. 1  
A n al ysis of t he pri m ar y v ari a ble 
T he pri mar y a n al ysis will be base d o n ass ess me nt of disease pr o gressi o n usi n g t he F A S. 
P F S will be s u m marise d usi n g t he Ka pla n- Meier ( K M) met h o d usi n g t he P R O C LI F E T E S T 
S A S pr oce d ure, w hi c h will i ncl u de a gra p h de picti n g t he s ur vi val c ur ve a n d esti mates of 
me dia n s ur vi val a n d ass o ciate d 9 5 % CI. Ce ns or e d pati e nts will be i n dicate d. I n a d diti o n, 
pr o gressi o n rat es a n d 9 5 % CIs at si x m o nt hl y i nter vals will be esti mate d usi n g t he K M 
met h o d. 
T he CI f or t he me di a n will be calc ulate d usi n g t he Br o o k me yer- Cr o wl e y met h o d. 
T he treat me nt stat us at pr o gressi o n of patie nts at t he ti me of a nal ysis will be s u m marise d. T his 
will i ncl u de t he n u m ber ( %) of patie nts w h o w ere o n ola pari b at t he ti me of pr o gressi o n, t he 
n u m ber ( %) of patie nts w h o disc o nti n ue d ola pari b pri or t o pr o gressi o n, t he n u m ber ( %) of 
patie nts w h o ha ve n ot pr o gresse d a n d wer e o n ola pari b or disc o nti n ue d ola pari b. T his will als o 
pr o vi de t he distri b uti o n of n u m ber of d a ys pri or t o pr o gressi o n f or t he p atie nts w h o ha ve 
disc o nti n ue d treat me nt.   
F or t he s B R C A m c o h ort t he detaile d R E CI S T t u m o ur assess me nt data will be list e d. 
S u b gr o u p a n al ysis 
T he pri mar y e n d p oi nt will be s u m marise d se paratel y f or eac h s u b gr o u p i n t he g B R C A m 
c o h ort as defi n e d bel o w: 
E val uati o n met h o d ( R E CI S T, N o n- R E CI S T, Cli nical/ S y m pt o matic, N ot a p plica ble).  T he 
e val uati o n met h o d at t he ti me of pr o gressi o n or at t he last p ost- baseli ne t u m o ur ass ess me nt 
f or ce ns ore d patie nts will be use d. F or patie nts wit h o ut a p ost- baseli ne t u m o ur ass ess me nt 
or w h o die d wit h o ut a pr o gressi o n t he cate g or y “ N ot a p plica ble” is use d. 
Li ne of t hera p y ( 1st li ne i.e. n o pri or c h e m ot hera p y use d i n 1 st li ne, b ut use d as 
a dj u va nt/ ne oa dj u va nt vs 2 n d li ne + i.e. pri or c h e m ot hera p y use d i n 1 st li ne, +/- pri or 
c he m ot hera p y i n a dj u va nt/ ne oa dj u va nt setti n g as c ollecte d i n t he Pre vi o us breast ca ncer 
c he m ot hera p y e C R F pa g e), s h o wi n g t he cate g ories “ 1st li ne” a n d “ 2 n d li ne +”.  
Pri or e x p os ure t o plati n u m-c o ntai ni n g t hera p y, i n t he Pre vi o us br east ca ncer c he m ot hera p y 
e C R F pa ge ( Yes vs. N o).  Cate g or y “ Y es” will be f urt her cl assifie d i nt o “ A dj u va nt/ Ne o-
a dj u va nt” a n d “ First li ne”. 
Li ne of t hera p y a n d pri or e x p os ure t o plati n u m-c o ntai ni n g t hera p y ( 1st li ne & Yes,  
    
1st li ne & N o,  2 n d li ne + & Yes,  2 n d li ne + & N o) 
Pri or e x p os ure t o a nt hrac ycli nes a n d rel ate d s u bsta nces ( Yes, N o) 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 4
Pri or e x p os ure t o ta xa n es ( Yes, N o) 
Pri or e x p os ure t o h or m o nal t hera p y ( Yes, N o) 
Pri or e x p os ure t o tar g ete d t hera p y ( Y es, N o) 
Pri or e x p os ure t o C D K 4/ 6 i n hi bit or (i ncl u di n g pal b ocicli b a n d ri b ocicli b) ( Yes, N o) 
Pri or e x p os ure t o pr otei n ki nase i n hi bit ors ( Yes, N o) 
H or m o ne stat us ( Estr o ge n-rec e pt or ( E R) a n d/ or pr o gester o ne-rece pt or ( P R) p ositi ve vs. 
tri ple ne gati ve) 
H or m o ne stat us a n d a g e at baseli ne gr o u p 2: 
o
o
o
E R a n d/ or P R p ositi ve & > 5 0 years 
o
o
o
Tri ple ne gati ve & > 5 0 y ears 
Me n o pa usal stat us at bas eli ne ( Pre-/ Peri- m e n o pa usal, P ost- me n o pa usal, N ot a p plica ble) 
H or m o ne stat us a n d me n o pa usal stat us at baseli ne: 
o
E R a n d/ or P R p ositi ve & Pre-/ Peri- me n o pa us al 
o
E R a n d/ or P R p ositi ve & P ost- me n o pa usal 
o
Tri ple ne gati ve & Pre-/ Peri- me n o pa us al 
o
Tri ple ne gati ve & P ost- me n o pa usal 
Re gi o n ( Asia, E ur o pe or N ort h A merica) 
B R C A m utati o n t y pe ( B R C A 1. B R C A 2. B ot h) 
Metastatic site: Visceral ( Yes, N o).  Viscer al i ncl u des: br ai n/ C N S, car di o v asc ular, 
res pirat or y, ascites, g astr oi ntesti nal, he patic (i ncl u di n g gall bla d der), ge nit o uri nar y, 
a dre nal, p ericar dial eff usi o n, perit o ne u m, ot her C N S, pa ncreas, s plee n, es o p h a g us, c ol o n 
a n d li ver. 
Metastatic site: B o ne a n d l oc o m ot or ( Yes, N o) 
Metastatic site: Li ver/ he p atic (i ncl u di n g gall bla d d er) ( Y es, N o) 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 5
Metastatic site: Res pirat or y ( Yes, N o) 
O nl y i n case of missi n g val ues a se p arate cate g or y “ Missi n g” will be a d de d f or a s u b gr o u p 
varia ble. 
Ka pla n- Mei er pl ots will be create d f or eac h of t he a b o ve s u b gr o u ps.  N o f or mal statistical 
c o m paris o ns will be perf or me d bet wee n t he s u b gr o u ps. 
T he P F S s u b gr o u p a nal ysis will be re peate d i n t he s u bset of E R a n d/ or P R p ositi ve patie nts. 
4. 2. 2  
A n al ysis of t he sec o n d ar y v ari a bles 
All efficac y data will be s u m marise d base d o n t he F A S. 
4. 2. 2. 1  
O ver all s ur vi v al 
O S will be a nal yse d usi n g K M met h o d ol o g y ( P R O C LI F E T E S T). A gra p h de picti n g t he 
s ur vi val c ur ve a n d esti mates of me dia n s ur vi v al a n d ass ociate d 9 5 % CI will pr o vi de d t o get her 
wit h O S rates at si x m o nt hl y i nter vals. C e ns ore d p atie nts will be i n dicate d. 
S u m maries of t he n u m ber a n d perce nta g e of patie nts w h o ha ve die d, t h ose w h o are ce ns or e d, 
t h ose still i n s ur vi val f oll o w- u p, t h ose l ost t o f oll o w- u p a n d t h ose w h o h a ve wit h dra w n 
c o nse nt will be pr o vi de d.  O verall s ur vi val f or t he g B R C A m c o h ort will als o be s u m marise d 
b y t he s u b gr o u ps descri b e d i n secti o n 4. 2. 1, i ncl u di n g t he Ka pla n- Mei er pl ots per s u b gr o u p, 
e xcl u di n g t he e val u ati o n met h o d, w hic h is n ot a p plica ble f or O S. 
I n a d diti o n, t he d urati o n of f oll o w- u p will be s u m marise d: 
I n ce ns or e d patie nts w h o are ali ve at t he last assess me nt bef ore D C O o nl y (e xcl u di n g 
t h ose w h o were l ost t o f oll o w- u p or w h o wit h dre w c o nse nt): Ti me fr o m dat e of first d ose 
of ola pari b t o date of ce ns ori n g ( date last k n o w n t o be ali ve bef ore t he D C O). 
I n all patie nts: Ti me fr o m date of first d ose of ol a pari b t o t he date of deat h (i.e. O S) or t o 
t he date of ce ns ori n g f or ce ns ore d p atie nts. 
4. 2. 2. 2  
Ot her ti m e-t o- e ve nt e n d p oi nts 
D o C R, D o R, T F S T, T S S T, T D T a n d P F S 2 will be a nal yse d usi n g K M m et h o d ol o g y. A gra p h 
de picti n g t he s ur vi val c ur ve a n d esti mates of me di a n s ur vi val a n d ass o ciate d 9 5 % CI will 
pr o vi de d t o get her wit h rates at si x m o nt hl y i nter vals. C e ns ore d patie nts will be i n dicate d. 
D o C R will be prese nte d f or t he patie nts i n t he g B R C A m c o h ort a n d D o R f or t he patie nts i n 
t he s B R C A m c o h ort. 
S u m maries of t he n u m ber a n d perce nta g e of patie nts w h o recei v e d a s u bs e q ue nt a nti-ca ncer 
t hera p y a n d a s u m mar y t a ble of first (a n d sec o n d) s u bse q ue nt a nti-ca n cer t hera pies will be 
pr o vi de d. D urati o n of cli nical res p o nse f or t he g B R C A m c o h ort will be prese nte d b y t he 
s u b gr o u ps descri be d i n s ecti o n 4. 2. 1 ( wit h o ut t he Ka pla n- Mei er pl ots b y s u b gr o u p), e xcl u di n g 
t he e val uati o n met h o d, w hic h is n ot a p plica ble f or D o C R. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 6
4. 2. 2. 3  
Cli nic al res p o nse r ate a n d o bjecti ve res p o nse r ate 
C R R a n d O R R will be s u m marise d as t he pr o p orti o n of patie nts as ha vi n g a res p o nse usi n g 
t he n u m ber of all patie nts i n t he F A S as t he de n o mi nat or.   Res p o nses occ urri n g after t he st art 
of s u bse q ue nt a nti-ca ncer t hera p y will n ot be i ncl u de d i n t he n u merat or. E x act bi n o mial 
( Cl o p per C, 1 9 3 4) 9 5 % CIs will be calc ulate d. C R R will be prese nte d f or t he patie nts i n t he 
g B R C A m c o h ort a n d O R R f or t he patie nts i n t he s B R C A m c o h ort. C R R f or t he g B R C A m 
c o h ort will be prese nt e d b y t he s u b gr o u ps descri b e d i n secti o n 4. 2. 1 ( wit h o ut t he Ka pla n-
Meier pl ots b y s u b gr o u p), e xcl u di n g t he e val u ati o n met h o d, w hic h is n ot a p plica ble f or C R R. 
4. 2. 2. 4  
Dise ase c o ntr ol r ate 
D C R at wee k 2 4 will be s u m marise d as t he pr o p orti o n of patie nts wit h n o e vi de nce of 
pr o gressi o n ( C R. P R, or S D) i n t he brai n fr o m t he Brai n assess me nt e C R F pa ges at or pri or t o 
wee k 2 4 usi n g t he n u m ber of patie nts wit h brai n m etastases at bas eli ne (fr o m t he Brai n 
metastases e val u ati o n baseli ne e C R F pa ge) as t he de n o mi nat or. E xact bi n o mial ( Cl o p per-
Pears o n) 9 5 % CIs will be c alc ulat e d. 
4. 2. 3  
A n al ysis m et h o ds of s afet y v ari a bles 
All safet y data will be s u m marise d base d o n t he F A S. 
4. 2. 3. 1 
E x p os u re  
T he f oll o wi n g s u m maries will be pr o d uce d: 
T otal ( or i nte n de d) e x p os ure t o ola pari b 
Act ual e x p os ur e t o ola pari b 
N u m ber of a n d reas o ns f or d ose i nterr u pti o ns of ola pari b 
N u m ber of a n d reas o ns f or d ose re d u cti o ns of ola pari b 
N u m ber of a n d reas o ns f or d ose m o dificati o ns of ola pari b 
R DI a n d PI D 
Ti me o n st u d y – defi ne d as t he earliest of t he t w o dates  
o
latest st u d y assess me nt or ola pari b d ose d at e 
o
st u d y ter mi nati o n date 
mi n us first ola pari b d ose date + 1. 
4. 2. 3. 2  
A d verse e v e nts 
O nl y T E A Es (see s ecti o n 3. 2. 3) will be s u m marise d.  A n y A E occ urri n g bef ore t he first d ose 
of ola pari b a n d A Es occ urri n g m ore t ha n 3 0 da ys after last d ose (i.e. A E o nset date > 3 0 da ys 
after d ate of last Ola p ari b d ose) will be liste d o nl y a n d n ot i ncl u de d i n t he s u m maries.  


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 7
A n o verall s u m mar y i nf or mati o n ta ble will be pr o d uce d i ncl u di n g t he n u m ber a n d perce nta ge 
of patie nts f or eac h cate g or y bel o w: 
All A Es 
All A Es ca usall y rel ate d t o ola pari b 
A Es wit h C T C A E gra de 3 or hi g her 
A Es wit h C T C A E gra de 3 or hi g her, ca usall y relat e d t o ola pari b 
A Es wit h o utc o me of deat h 
A Es wit h o utc o me of deat h, ca usall y relate d t o ola pari b 
All S A Es 
All S A Es ca usall y relate d t o ola pari b 
A Es lea di n g t o disc o nti n uati o n of ola pari b 
A Es lea di n g t o disc o nti n uati o n of ola pari b, ca usall y relate d t o ola pari b 
A Es lea di n g t o d ose m o dific ati o n (eit her re d ucti o n or i nterr u pti o n) of ola p ari b 
A Es lea di n g t o d ose m o dific ati o n of ola pari b, ca us all y relate d t o ola pari b 
A Es lea di n g t o d ose re d u cti o n of ola pari b 
A Es lea di n g t o d ose re d u cti o n of ola pari b, ca usall y relate d t o ola pari b 
A Es lea di n g t o d ose i nterr u pti o n of ola pari b 
A Es lea di n g t o d ose i nterr u pti o n of ola pari b, ca usall y relate d t o ola pari b 
A n o verall s u m mar y of t he n u m ber of e pis o des i n eac h of t h e a b o ve cate g ories will als o be 
ta b ulate d. 
F or eac h of t h ese cate g ories s u m maries will be prese nte d b y s yste m or ga n class ( S O C) a n d 
P T, wit h t he e xce pti o n of ca usall y rel ate d A Es lea di n g t o d ose m o dificati o n or re d ucti o n or 
i nterr u pti o n a n d ca us all y relate d A Es wit h o utc o m e deat h. 
A tr u ncate d A E s u m mar y ta ble of m ost c o m m o n A Es, s h o wi n g all e ve nts t hat occ ur i n at least 
5 % of patie nts will be s u m marise d b y decreasi n g fre q ue n c y of P T. 
A E a n d S A E e ve nt rates (i.e., e x p os ure a dj uste d i nci de nce of patie nts wit h a n A E/ S A E) will 
als o be s u m marize d b y P T wit hi n eac h S O C. A E e ve nt r ates will be calc ulat e d as t he n u m ber 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 8
of patie nts wit h at least o ne e ve nt di vi de d b y t he t otal ti me at ris k, i.e. t he n u m ber of da ys of 
t otal ( or i nte n de d) e x p os ure (se e secti o n 3. 2. 1) t o ola pari b s u m me d o ver all patie nts. T his rate 
is t he n m ulti plie d b y 1 0 0 0 t o prese nt e ve nts per 1 0 0 0 patie nt years.  
T he n u m ber of p atie nts e x perie nci n g eac h A E will be s u m marise d b y S O C, P T a n d w orst 
C T C A E gra de. 
N a use a a n d v o miti n g 
Rates a n d w orst C T C A E gra de of n a usea/ v o miti n g, as i de ntifie d b y me dical re vi e w of t h e A E 
u ni q ue ter ms, will be s u m marise d o ver ti me a n d als o acc or di n g t o w het her t he patie nt recei ve d 
a ntie metic t hera p y, as i de ntifie d b y me dical re vie w of t he c o nc o mita nt me dicati o n ter ms, 
ta ki n g i nt o acc o u nt t he w orst C T C A E gra de of n a usea/ v o miti n g at t he ti me of a d mi nistrati o n. 
A d verse e v e nts of s peci al i nterest  
A d verse e ve nts of s pe cial i nterest ( A E SI) f or ola p ari b ar e: 
M yel o d ys plastic s y n dr o me ( M D S) / Ac ute m yel oi d le u kae mia ( A M L) 
Ne w pri mar y m ali g na nc y ( ot her t ha n M D S/ A M L) 
P ne u m o nitis 
S u m maries of t he a b o ve me nti o ne d A E SIs, after me dical re vie w of t he A E u ni q ue ter ms, will 
i ncl u de n u m ber ( %) of p atie nts w h o ha ve: 
At least o ne A E SI 
At least o ne A E SI ca usall y relate d t o ola pari b 
At least o ne A E SI lea di n g t o disc o nti n uati o n of ola pari b 
I n a d diti o n, A Es, A Es wit h o utc o me of deat h a n d S A Es will be liste d. 
A n ae mi as a n d bl o o d tr a nsf usi o ns 
A Es of a nae mia will be s u m marise d b y w orst C T C A E gra de, s h o wi n g als o t he n u m ber (a n d 
%) of affecte d patie nts w h o recei v e d a bl o o d tra nsf usi o n. 
Ot her s u b gr o u ps of A Es 
T he A E o ver vi e w ta ble will be re peat e d f or t he f oll o wi n g s u b gr o u ps of A Es, w hic h will be 
defi ne d bas e d o n t he preferre d t er ms: 
A nae mia gr o u p e d ter m 
Fati g ue / ast he nia gr o u pe d ter m 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
3 9
Le u k o pe nia gr o u p e d ter m 
L y m p h o pe nia gr o u pe d ter m 
Na usea gr o u pe d ter m 
Ne utr o pe nia gr o u pe d ter m 
T hr o m b oc yt o pe nia gr o u p e d ter m 
V o miti n g gr o u pe d ter m 
C O VI D- 1 9 a d verse e ve nts 
C o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o ns are defi ne d as a d verse e ve nts occ urri n g d uri n g 
t he pa n de mic ti mefra me ( p ost 1 1- Mar- 2 0 2 0) wit h preferre d t er m a n d l o wer le vel ter m wit hi n 
t he searc h criteria s pecifi e d i n t he A Z O nc ol o g y P a n de mic C S R H L D Ta ble a n d Listi n g 
Te m plates v 1. 0.   
C O VI D- 1 9 ass o ciate d A Es are c o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o n A Es pl us all ot her 
A Es of t he sa me p atie nt wit h o nset i n t he peri o d fr o m < 7 da ys pri or t o start u ntil < 3 0 da ys 
after start of a c o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o n A E. 
Patie nts wit h c o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o n a n d patie nts wit h c o nfir me d / 
s us pecte d C O VI D- 1 9 i nfecti o n w h o die d will be s u m marise d.   
C o nfir me d or s us pecte d C O VI D- 1 9 i nfecti o n A Es, C O VI D- 1 9 ass o ciate d A Es a n d all A Es of 
patie nts wit h c o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o n will be liste d. 
4. 2. 3. 3  
De at hs 
A s u m mar y of deat hs will be pr o vi de d wit h n u m ber a n d perce nta ge of p atie nts, cate g orise d as: 
Relate d t o disease u n der i n vesti gati o n o nl y ( deat hs > 3 0 da ys aft er last ola p ari b d ose) 
A E wit h o utc o me = de at h o nl y ( A E o nset > 3 0 da ys after last ola p ari b d ose) 
after last ola p ari b d ose) 
Relate d t o disease u n der i n vesti gati o n a n d wit h A E o utc o me = deat h ( deat hs > 3 0 da ys 
after last ola p ari b d ose) 
Deat hs > 3 0 d a ys after last ola pari b d ose, u nrel at e d t o A E or disease u n d er 
i n vesti gati o n 
Patie nts wit h u n k n o w n reas o n f or deat h 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
4 0
All deat hs will be liste d. 
4. 2. 3. 4 
L a b or at or y e v al u ati o ns 
La b orat or y d ata o btai ne d u p u ntil t he 3 0 da y safet y f oll o w- u p visit will be i ncl u de d i n t he 
s u m mar y ta bles. A bs ol ute val ues a n d c ha n ge fr o m baseli ne f or all c o nti n u o us hae mat ol o g y 
la b orat or y para meters will be s u m marise d b y a nal ysis visit. 
S hift ta bles f or c ha n g e i n C T C A E gra de fr o m baseli ne t o t he ma xi m u m p ost- baseli ne C T C A E 
gra de will be pr o d u ce d f or hae mat ol o g y para meters, c o nsi deri n g b ot h c ha n ges t o t he 
mi ni m u m p ost- baseli ne val ue (a n ae mia, le u k o p e nia, l y m p h o pe nia, ne utr o pe nia, 
t hr o m b oc yt o pe nia) a n d c ha n ges t o t he ma xi m u m p ost- baseli ne val ue (i ncr ease d hae m o gl o bi n, 
le u k oc yt osis, i ncreas e d l y m p h oc yte c o u nt).  T he l a b orat or y para met ers f or w hic h C T C gra de 
s hift o ut p uts will be pr o d uce d are: hae m o gl o bi n, l e u k oc ytes, l y m p h oc ytes ( a bs ol ute c o u nt), 
ne utr o p hils (a bs ol ute c o u nt) a n d platelets. 
Cli nical c he mistr y res ults will be list e d o nl y as t he y are n ot ma n dat or y at e v er y visit.   
H y's l a w 
T o assess H y’s la w criteria t he f oll o wi n g cate g ories of ma xi m u m p ost- baseli ne A L T a n d A S T 
will be ta b ulate d vers us c ate g ories of ma xi m u m p ost- baseli ne t otal bilir u bi n, base d o n 
m ulti ples of t he u p per li mit of t he n or mal ra n ge ( U L N): 
A L T < 3 * U L N 
A S T < 3 * U L N 
T otal bilir u bi n < 2 * U L N 
Scatter pl ots will s h o w A L T a n d A S T vers us t otal bilir u bi n as m ulti ples of U L N.  Data 
c ollecte d o n t he H y’s La w e C R F pa ge will be liste d. 
4. 2. 3. 5 
Electr oc a r di o gr a m ( E C G) 
E C G data will be liste d o nl y. 
4. 2. 3. 6  
Vit al si g ns 
Vital si g ns data ( bl o o d pr ess ure, p ulse, te m perat ure) will be list e d o nl y. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
4 1
4. 2. 3. 7 
Pre g n a nc y test 
P ositi ve pre g na nc y test res ults will be liste d o nl y. 
4. 2. 3. 8  
O ver d ose res ults 
O ver d ose d ata will be liste d o nl y. 
4. 2. 4  
A n al ysis m et h o ds of de m o gr a p h y a n d b aseli ne c h ar acteristics v ari a bles 
4. 2. 4. 1 
P atie nt dis p ositi o n 
T he t otal n u m ber of patie nts scree ne d (a n d s cree n fail ures), p atie nts e nr olle d, patie nts n ot 
assi g ne d t o ola pari b, pati e nts w h o recei ve d a n y ol a pari b, patie nts o n g oi n g ola pari b at D C O,  
patie nts w h o disc o nti n ue d ola pari b a n d t he reas o n f or disc o nti n uati o n, patie nts o n g oi n g i n t he 
st u d y, patie nts w h o ter mi nate d st u d y a n d reas o ns f or ter mi nati o n will be s u m marise d. 
T he reas o ns f or n ot bei n g e nr olle d will be s u m marise d f or scree ne d b ut n ot e nr olle d patie nts. 
T he n u m ber a n d p erce nta ge of patie nts i ncl u de d i n all t he a nal ysis p o p ulati o ns a n d t he n u m ber 
of patie nts recr uite d b y re gi o n, c o u ntr y a n d ce ntre will be als o prese nte d. 
4. 2. 4. 2 
Pr ot oc ol de vi ati o ns 
All i de ntifie d i m p orta nt pr ot oc ol de viati o ns will be s u m maris e d f or t he F A S. T his s u m mar y 
will be re peat e d f or i m p orta nt pr ot oc ol de viati o ns relate d t o C O VI D- 1 9 a n d i m p orta nt 
pr ot oc ol de viati o ns n ot relate d t o C O VI D- 1 9.    
I m p ort a nt pr ot oc ol de viati o ns (relate d or n ot r elate d t o C O VI D- 1 9) a n d pr ot oc ol de viati o ns 
relate d t o C O VI D- 1 9 (i m p orta nt or n ot i m p orta nt) will be liste d. 
4. 2. 4. 3  
De m o gr a p hics a n d ot her b aseli ne c h ar acteristics 
De m o gra p hic a n d baseli n e patie nt c haract eristics will be s u m marise d f or t he F A S as f oll o ws: 
-
a ge ( years) 
o
as c o nti n u o us varia ble  
o
o
-
se x 
-
race 
-
et h nicit y 
-
wei g ht ( k g) 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
4 2
o
as c o nti n u o us varia ble 
o
Nic oti ne use, le vel of e d ucati o n a n d me n o pa us al stat us will be s u m maris e d. 
4. 2. 4. 4  
Me dic al/s ur gic al hist or y 
All me dical a n d s ur gical hist or y will be s u m marise d se par atel y ( n u m ber a n d perce nt a ge of 
patie nts) f or t he F A S b y S O C a n d P T. 
Breast ca n cer s ur gical hist or y will be s u m marise d usi n g t he e C R F cate g ories. 
4. 2. 4. 5  
Dise ase hist or y 
T he f oll o wi n g disease c h aract eristics will be s u m marize d f or all patie nts i n t he F A S: 
Disease c h aracteristics at baseli ne (ti me fr o m ori gi nal dia g n osis, ti me fr o m first 
dia g n osis of metastatic dise ase, pri mar y t u m o ur lateralit y at dia g n osis, hist ol o g y t y pe 
at dia g n osis, pri mar y t u m o ur at dia g n osis, re gi o nal l y m p h n o des at di a g n osis, dista nt 
metastases at dia g n osis, t u m o ur gra de at dia g n osis, sta ge/ A merica n J oi nt C o m mittee 
o n Ca ncer [ AJ C C] sta ge at dia g n osis, E C O G) 
E xte nt of disease u p o n e ntr y t o st u d y (e val uati o n met h o d, ra di ol o gical assess me nt, 
metastatic/l ocall y a d va n c e d, site of metastatic disease) 
Pre vi o us disease-relate d treat me nt m o dalities b y a nat o mical t hera p e utic c h e mical 
( A T C) classificati o n a n d preferre d gr o u p. Pre vi o us disease-relate d treat me nt 
m o dalities  will als o b e prese nte d b y treat me nt stat us a n d preferre d gr o u p as well as b y 
patie nt re gi me n. 
Pre vi o us breast ca ncer t hera p y (c he m ot hera p y, plati n u m c o m p o u n ds a n d ot her 
t hera pies)  
Rece pt or stat us f or E R/ P R ( ne gati ve/ p ositi ve) 
Rece pt or stat us f or H E R 2 ( ne gati ve/ p ositi ve) 
Fa mil y hist or y of ca n cer 
B R C A 1/ 2 ge ne stat us ( B R C A 1/ B R C A 2/ b ot h) 
4. 2. 4. 6  
C o nc o mit a nt pr oce d ure/s ur ger y 
All c o nc o mita nt pr oce d ures/s ur geries will be s u m marise d ( n u m ber a n d perce nta ge of patie nts) 
f or t he F A S b y S O C a n d P T. 


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
4 3
4. 2. 4. 7  
C o nc o mit a nt m e dic ati o n 
C o nc o mita nt me dicati o n will be s u m marise d ( n u m ber a n d perc e nt a ge of patie nts) b y A T C 
classificati o n c o de f or t h e F A S. 
M ore o ver, t he f oll o wi n g c o nc o mita nt me dicati o ns or t hera pies will be s u m marize d: 
Disall o we d c o nc o mita nt me dicati o ns (see s ecti o n 7. 7 of t he C S P a n d secti o n 2. 2 of t he 
S A P) 
P ost-st u d y treat me nt (s u bse q ue nt) a nti-c a ncer t her a pi es ( p ost-st u d y treat me nt 
me dicati o ns are t h ose wit h a start date after t he l ast d ose date of ola p ari b rec or de d i n 
t he P ost st u d y dr u g disc o nti n uati o n ca ncer t h era p y e C R F pa ge) 
First p ost-st u d y treat me nt (s u bse q ue nt) a nti-ca ncer t hera pies 
Pri or me dicati o ns will be liste d o nl y. 
4. 2. 4. 8  
C o vi d- 1 9 d at a 
Disc o nti n uati o ns of st u d y treat me nt or st u d y d ue t o C O VI D- 1 9 will be s u m marise d wit hi n t he 
patie nt dis p ositi o n ta ble.  
I m p ort a nt pr ot oc ol de viati o ns relate d t o C O VI D- 1 9 will be s u m marise d se p aratel y, a n d all 
C O VI D- 1 9 relate d pr ot o c ol de viati o ns will be liste d.   
T he n u m ber of p atie nts e nr olle d bef ore a n d after t he start of t he C O VI D- 1 9 pa n de mic will be 
s u m marise d, t o get her wit h t he n u m ber of patie nts n o l o n ger i n t he st u d y a n d o n g oi n g i n t he 
st u d y at t he start of t he p a n de mic.   
T he f oll o wi n g C O VI D- 1 9 st u d y disr u pti o ns will be s u m marise d: 
St u d y dr u g i m pacte d b y C O VI D- 1 9 
St u d y treat me nt disc o nti n uati o n d ue t o C O VI D- 1 9 
St u d y disc o nti n uati o n d ue t o C O VI D- 1 9 
C o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o ns are defi ne d as a d verse e ve nts occ urri n g d uri n g 
t he pa n de mic ti mefra me ( p ost 1 1- Mar- 2 0 2 0) wit h preferre d t er m a n d l o wer le vel ter m wit hi n 
t he searc h criteria s pecifi e d i n t he A Z O nc ol o g y P a n de mic C S R H L D Ta ble a n d Listi n g 
Te m plates v 1. 0.   
C O VI D- 1 9 ass o ciate d A Es are c o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o n A Es pl us all ot her 
A Es of t he sa me p atie nt wit h o nset i n t he peri o d fr o m < 7 da ys pri or t o start u ntil < 3 0 da ys 
after start of a c o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o n A E. 
Patie nts wit h c o nfir me d / s us pecte d C O VI D- 1 9 i nfecti o n a n d patie nts wit h c o nfir me d / 
s us pecte d C O VI D- 1 9 i nfecti o n w h o die d will be s u m marise d. 




St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
4 5
Pre vi o us disease-relate d treat me nt m o dalities b y A T C classificati o n a n d pr eferr e d 
gr o u p / b y patie nt re gi me n 
 
Pre vi o us breast ca ncer c h e m ot hera p y 
Pre vi o us breast ca ncer c h e m ot hera p y plati n u m c o m p o u n ds   
Pre vi o us breast ca ncer ot her t her a pies 
De m o gra p hics, dise ase c haract eristics, pre vi o us disease-relate d treat me nt m o dalities 
b y A T C classificati o n a n d preferre d gr o u p a n d t he s u b gr o u ps descri be d i n s ecti o n 
4. 2. 1 will als o be s u m marise d b y h or m o ne stat us a n d me n o pa usal st at us at baseli ne f or 
t he g B R C A m c o h ort.  
S u m mar y of P F S 
P F S s u b gr o u p a nal ysis 
P F S s u b gr o u p a nal ysis f or E R a n d/ or P R p ositi ve pati e nts  
D o C R f or t he g B R C A m c o h ort 
T F S T  
T D T  
C R R f or t he g B R C A m c o h ort 
C R R s u b gr o u p a nal ysis 
D urati o n of e x p os ur e a n d ti me o n st u d y 
O verall s u m mar y of A Es  
 
S A Es b y S O C a n d P T  
M ost c o m m o n A Es 
 
A Es b y S O C, P T a n d ma xi m u m re p orte d C T C A E gra de  
 
A Es of s pe cial i nter est 
A Es of a nae mia a n d bl o o d tra nsf usi o ns 
T he f oll o wi n g fi g ures w ere pre p are d f or t he i nteri m a nal ysis: 
Ka pla n- Mei er pl ots f or P F S, D o C R, T F S T, T D T f or t he g B R C A m c o h ort  


St atistical A nal ysis Pla n  
St u d y C o d e D 0 8 1 6 C 0 0 0 1 8 
E diti o n N u m ber 3. 0 
Date 1 4- Se p- 2 0 2 1 
4 6
Ka pla n- Mei er pl ots f or P F S b y s u b gr o u ps f or t he g B R C A m c o h ort. 
T he fi nal a n al ysis will be perf or me d at t he e n d of t he st u d y w he n  a p pr o xi m atel y 1 3 0 patie nts 
ha ve die d, at w hi c h p oi nt t he P F S a nal ysis will be u p date d a n d all o ut p uts descri be d i n t his 
S A P will be pr o d uce d. 
6.  
C H A N G E S O F A N A L Y SI S F R O M P R O T O C O L 
N ot a p plica ble. 
7.  
R E F E R E N C E S 
Cl o p per C, P. E. ( 1 9 3 4). T he use of c o nfi de nce or fi d ucial li mits ill ustrate d i n t he case of t h e 
bi n o mial. Bi o metrik a , 2 6: 4 0 4- 4 1 3. 
Eise n ha uer E A, T. P. ( 2 0 0 9). Ne w res p o nse e v al u ati o n criteria i n s oli d t u m o urs: re vise d 
R E CI S T g ui deli ne ( versi o n 1. 1). E ur J C a ncer , 4 2( 2): 2 2 8- 4 2 7. 
8.  
A P P E N DI X  
N ot a p plica ble.