Descriptive Analyses of Clinical Characteristics and Treatment Patterns of Breast Cancer Patients Initiating Palbociclib (Ibrance(Registered)) Treatment in Japan by Using MDV Database
Conditions: Breast Cancer
Sponsor: Pfizer

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 of 2 5
N O N- I N T E R V E N TI O N A L ( NI) S T U D Y P R O T O C O L
St u d y i nf or m ati o n
Title
Descri pti ve A nal y ses of Cli nical 
C haracteristics a n d Treat me nt Patter ns of 
Breast Ca ncer Patie nts I nitiati n g Pal b ocicli b 
(I bra nce® ) Treat me nt i n Ja pa n b y  Usi n g 
M D V D ata base
Pr ot oc ol n u m ber
A 5 4 8 1 1 1 5
Pr ot oc ol versi o n i de ntifier
4 . 0 
D ate
3 1 Marc h 2 0 2 1
Acti ve s u bst a nce
Pal b ocicli b
Me dici n al pr o d uct
I bra nce
Rese arc h q uesti o n a n d o bjecti ves
Pal b ocicli b (I bra nce ® ) was la u nc he d i n 
Ja pa n i n Dece m ber 2 0 1 7 . T his st u d y will 
des cri be t he c haracteristics of patie nts 
i nitiati n g treat me nt wit h pal b ocicli b b y  usi n g 
M e dical D ata V isi o n ( M D V) data base (clai m 
data base) i n ter ms of de m o gra p hic a n d 
cli nical c haracteristics, real -w orl d utilizati o n 
of pal b ocicli b ( e. g. li ne of t hera py, 
c o nc o mita nt use of ot h er
c he m ot hera p y/ e n d ocri ne t hera py/ s u p p orti ve 
dr u gs), a m o n g t he patie nts wit h breast 
ca ncer f oll o wi n g its la u nc h i n Ja pa n.
A ut h or
 P h. D.
 
 Pfizer Ja pa n
3- 2 2- 7, Y o y o gi, S hi b u y a-k u, T o k y o 1 5 1-
8 5 8 9 Ja pa n
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer.  E xce pt as ot her w ise a gree d t o i n 
writi n g, b y acce pti n g or re vie wi n g t his d oc u me nt, y o u a gree t o h ol d t his i nf or mati o n i n c o n fi de nce a n d n ot 
co p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or use it f or u na ut h orize d p ur p oses.  I n 
t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)
P P D
P P D

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 2 of 2 5
1. T A B L E O F C O N T E N T S
1. T A B L E O F C O N T E N T S .......................................................................................................2
2. LI S T O F A B B R E VI A T I O N S................................................................................................4
3. R E S P O N SI B L E P A R TI E S ....................................................................................................5
4. A B S T R A C T ...........................................................................................................................6
5. A M E N D M E N T S A N D U P D A T E S .......................................................................................7
6. MI L E S T O N E S .......................................................................................................................8
7. R A TI O N A L E A N D B A C K G R O U N D.................................................................................. 9
8. R E S E A R C H Q U E S TI O N A N D O BJ E C TI V E S .................................................................1 0
9. R E S E A R C H M E T H O D S................................ ....................................................................1 1
9. 1. St u d y  desi g n............................................................................................................1 1
9. 2. Setti n g ......................................................................................................................1 1
9. 2. 1. I ncl usi o n criteria .........................................................................................1 2
9. 2. 2. E xcl usi o n criteria ........................................................................................1 2
9. 3. Varia bles ..................................................................................................................1 2
9. 4. Data s o urces ............................................................................................................1 3
9. 5. St u d y size ................................................................................................................1 4
9. 6. Data ma na ge me nt ....................................................................................................1 4
9. 7. Data a nal y sis ...........................................................................................................1 4
9. 7 . 1. Statistical me t h o ds......................................................................................1 4
9. 8. Q ualit y  c o ntr ol.........................................................................................................1 7
9. 9. L i mitati o ns of t he researc h met h o ds .......................................................................1 8
9. 1 0. Ot her as pects .........................................................................................................1 8
1 0. P R O T E C TI O N O F H U M A N S U BJ E C T S ........................................................................1 8
1 0. 1. Patie nt i nf or mati o n................................ ................................................................1 8
1 0. 2. Patie nt c o nse nt .......................................................................................................1 8
1 0. 3. I nstit uti o nal re vie w b oar d (I R B)/I n de pe n de nt et hics c o m mittee (I E C) ................1 8
1 0. 4. Et hical c o n d uct of t he st u d y ..................................................................................1 8
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S ......................................................................................................................1 9
1 2. P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S ........2 0
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 3 of 2 5
1 3. R E F E R E N C E S ..................................................................................................................2 0
1 4. LI S T O F T A B L E S .............................................................................................................2 1
1 5. LI S T O F FI G U R E S ................................ ...........................................................................2 1
A N N E X 1 . A D DI TI O N A L IN F O R M A TI O N .........................................................................2 1
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 4 of 2 5
2. LI S T O F A B B R E VI A TI O N S
A b bre vi ati o n
Defi niti o n
A B C
A d va nce d b reast ca ncer
A E
A d verse e ve nt
A E M
A d verse e ve nt m o n it ori n g
A I
Ar o matase i n hi bit or
A T C
A nat o mical thera pe utic che mical classificati o n sys te m
C D K
C y cli n-de pe n d e nt ki nase
CI
C o n fi de nce i nter val
CI O M S
C o u ncil f or I nter nati o nal Or g a nizati o ns of Me dical Scie nces
C S S
Cli nical St u d y  S up p ort, I nc.
D N A
De o x yr i b o n ucleic aci d
D P C
Dia g n osis Pr oce d ure C o m bi nati o n
E M A
E ur o pea n Me dici nes A ge nc y
E N Ce P P
E ur o pea n Net w or k of Ce ntres f or P ha r mac oe pi de mi ol o g y a n d 
P har mac o vi gila nce
E R
Estr o ge n rece pt or
F D A
F o o d a n d Dr u g A d mi nistrati o n
G -C S F
Gra n ul oc y te-C ol o n y  Sti m ulati n g Fact or
G E P
G o o d E pi de mi ol o gical Practice
G P P
G o o d P har mac oe pi de mi ol o g y  Practices
H E R 2
H u ma n e pi der mal gr o wt h fact or rec e pt or 2
H R
H or m o ne rece pt or
I C D
I nter nati o nal Statistical Classificati o n of Diseases a n d Relate d Healt h 
Pr o ble ms
I C D-1 0
I C D 1 0 t h re visi o n
I EA
I nter nati o nal E pi de mi ol o gical Ass ociati o n
I E C
I n de pe n de nt et hics c o m mittee
I RB
Ins tit uti o nal Re vie w B o ar d
I S P E
I nternati o nal S ociet y f or P har mac oe pi de mi ol o g y
I S P O R
I nter nati o nal S ociety f or P har mac oec o n o mics a n d O utc o mes Researc h
L H -R H
L utei nizi n g H or m o ne -Releasi n g H or m o ne
M D V
Me dical Data Visi o n
C o ., Lt d.
N E
N ot esti ma ble
NI S
N o n -i nter ve nti o nal st u d y
P F S
P r ogressi o n -free s urvi v al
Q C
Q ualit y  c o ntr ol
S A P
Statistical A nal y sis Pla n
T T F
T i me t o treat me nt fail ure 
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 5 of 2 5
3. R E S P O N SI B L E P A R TI E S
N a m e, de gree(s)
J o b Title
Affili ati o n
A d dress
 P h. D.
 
 
 Pfizer Ja pa n
3- 2 2 -7, Y o y o gi, S hi b u ya -k u, 
T o k y o 1 5 1 -8 5 8 9 Ja pa n
 P h. D.
 
Pfizer Ja pa n
 
3- 2 2 -7, Y o y o g i, S hi b u ya -k u, 
T o k y o 1 5 1 -8 5 8 9 J apa n
 
 
 Pfizer Ja pa n
3- 2 2 -7, Y o y o g i, S hi b u ya-k u, 
T o k y o 1 5 1 -8 5 8 9 Ja pa n
 Pfizer Ja pa n
3- 2 2 -7, Y o y o gi, S hi b u ya -k u, 
T o k y o 1 5 1 -8 5 8 9 Ja pa n
P h. D.
Cli nical St u d y
S u p p ort I nc.
2 F, 1 -1 1 -2 0 Ni s hi ki, Na ka-
k u, Na g o ya 4 6 0 -0 0 0 3 Ja pa n
P h. D. 
Cli nical St u d y
S u p p ort I nc.
2 F, 1 -1 1 -2 0 Ni s hi ki, Na ka -
k u, Na g o ya 4 6 0 -0 0 0 3 Ja pa n
, M. D., 
P h. D.
Aic hi Ca ncer Ce nter 
H os pital
1- 1 Ka n o k o d e n, C hi k usa -k u, 
Na g o ya 4 6 4 -8 6 8 1 Ja pa n
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 6 of 2 5
4. A B S T R A C T

Title : 
Descri pt i ve A nal yses of Cli nical C har acteristics a n d Treat me nt Patte r ns of Breast Ca ncer 
Patie nts I nitiati n g Pal b ocicli b (I bra nce ® ) Treat me nt i n Ja pa n by U si n g Me dical Data 
Visi o n C o., L t d.(M D V ) Data base (versi o n 3. 0, 0 1 Dece m ber 2 0 1 9 )
 P h. D.
, Pfizer Ja pa n 3- 2 2- 7, Y o y o gi, S hi b u y a-k u, T o k y o 1 5 1 - 8 5 8 9 
Ja pa n 

Ra ti o nale a n d bac k gr o u n d:
Pal b ocicli b is t he first C y cli n- de pe n de nt ki nase (C D K ) 4/ 6 i n hi bit or a p pr o ve d i n Ja pa n i n
c o m bi nati o n wit h e n d o cri ne t hera p y f or treat me nt of h or m o ne rece pt or p osit i ve/ h u ma n 
e pi der mal gr o wt h fact or rece pt or 2 ne gati ve ( H R +/ H E R 2-) a d va nce d breast ca ncer. 
Pal b ocicli b was a p pr o ve d i n Se pte m ber 2 0 1 7 a n d la u nc he d in Dece m ber 2 0 1 7. I n t he 
Ja pa nese pac ka ge i nsert f or pal b ocicl i b, t he data f or o nl y 5 9 Ja pa nese patie nts w h o were 
a d mi nistrate d pal b ocicli b i n P A L O M A -2 a n d P A L O M A -3 st u dies is d escri be d. Als o 
neit her treat me nt li ne n or c o nc o mita nt treat me nt dr u g is defi ne d i n t he Ja pa nese pac ka ge 
i nsert a n d t here is n o data f or treatme n t se q ue nce of pal b ocicli b. T h us retrie vi n g d a ta 
fr o m real w orl d setti n g f or pal b ocicli b is necessar y t o clarif y t he treat me nt patter n of 
pal b ocicli b i n Ja pa n f or t he a p pr o priate use a n d t his n o n-i nter ve nti o nal st u d y was pla n ne d.
T his st u d y  ai ms to descri be patie nt de m o gra p hic, tr eatme nt patter ns a n d treat me nt
d u rati o n a m o n g H R +/ H E R 2- a d va nce d breast ca ncer(A B C) pati e nts w h o i nitiate d 
pal b ocicli b. I n a d diti o n, t his st u d y  will descri be s u bse q ue nt treat me nt patter ns a n d 
treat me nt d urati o n after palb ocicli b -base d t hera p y.   In a d diti o n, t h is st u d y will descri be 
h o w trea t ment para di g m c ha n ges wit h t he la u nc h of ne w tr eat ment o pti o n, C D K 4/ 6 
i n hi bit or.

Researc h q uesti o n a n d o bjecti ves : 
T he pri mar y o bjecti ve of t his st u d y  is t o descri be patie nt de m o grap hics, treat me nt 
patter ns a n d treat me nt d urati o n of pal b ocicli b, a n d s u bs e q ue nt treat me nt patter ns a n d 
treat me nt d urati o n after pal b ocicli b-base d t hera p y a m o n g a d va nce d metastatic breast 
ca ncer patie nts i n Ja pa n i nitiati n g treat me nt wit h pal b ocicli b f oll o w i n g dr u g la u nc h i n 
Ja pa n ( 1 5 Dec e m ber 2 0 1 7). 
T he sec o n dar y  o bjecti ve of t he st u d y is t o descri be patie nt de m o gra p hics, treat me nt 
patter ns of A B C patie nts a n d treat me nt d urati o n of e n d ocri ne t hera p y , a n d s u bse q ue nt 
treat me nt patter ns a n d treat me nt d urati o n after e n d ocri ne t hera py a m o n g a d va nce d 
metastatic breast ca ncer fe male patie nts t o a d dress treat me nt para di g m c ha n ges i n Ja pa n 
wit h t he la u n c h of ne w treat me nt o pti o n.

St u d y  desi g n: 
T his is a re tr os pecti ve o bser vati o nal st u d y f oc usi n g o n patie nts dia g n os e d wit h breast 
ca ncer i n Ja pa n usi n g de -i de ntifie d clai m data fr o m M D V data base. Patie nts w h o meet 
t he i ncl usi o n criteria will be retr os p ecti vel y selecte d fr o m M D V data b ase. 
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)
P P D
P P D

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 7 of 2 5

P o p ulati o n : 
Ja pa nese patie nts di a g n ose d wit h breast ca nc er a n d w h ose data were e ntere d i nt o M D V 
data base fr o m A pril 2 0 0 8 will be i ncl u de d i n t his st u d y .

Varia bles : 
A ge , Ge n der, Wei g ht , Hei g ht, Pal b ocicli b treat me nt date, Pal b ocicli b d ail y d ose , 
Pal b ocicli b treat me nt d urati o n, E n d ocri n e t hera p y c o m bi ne d wit h pal b ocicli b , Treat me nt 
patter n of eac h li nes of t hera p y, C he m ot hera p y  treat me nt patter n , E n d oc ri ne t hera py 
treat me nt pattern , E n d ocri ne t hera p y  treat me nt d urati o n, Ti me t o treat me nt fail ure , G-
C S F treat me nt date , A nti bi oti cs treat me nt date , Bl o o d test date, D urati o n of t he a dj u va nt 
t hera py, D urati o n fr o m s ur ger y t o t he starti n g of 1st li ne t hera p y

St u d y  size: 
T his is a descri pti ve st u d y a n d sa m ple size a n d p o wer calc ulati o ns are n ot a p plica ble.  All 
eli gi ble patie nts wit h breast ca ncer dia g n osis a n d w h o recei ve d e n d ocri ne t hera p y dr u gs 
a n d w h o di d n’t recei ve anti -H E R 2 t hera p y dr u gs ( def i ned a s H R +/ H E R 2- breast ca ncer) 
will b e i ncl u de d i n t he a nal ysis. Accor di n g t o a preli mi nar y  feasi bilit y assess me nt, t he 
n u m ber of H R +/ H E R 2 - breast ca ncer patie nts is 1 0, 3 1 2 4 .

Data a nal y sis: 
T he pri mar y o bjecti ve of t his st u d y is t o descri be patie nt de m ogra p hi cs, treat me nt 
patter ns a n d treat me nt d urati o n of pal b ocicli b, a n d s u bse q ue nt treat me nt patt er ns a n d 
treat me nt d urati o n after pal b ocicli b-base d t hera p y a m o n g t he a d va nce d metastatic breast 
ca ncer fe male patie nts in Ja pa n i ni tiati n g treat me nt wit h pal boci clib f oll o wi n g dr u g 
la u nc h i n Ja pa n. T he sec o n dar y  o bjecti ve of t he st u d y is t o descri be patie nt de m o gra p hics, 
treat me nt patter ns of A BC patie nts a n d treat me nt d urati o n of e n d ocri ne t hera p y, a n d 
s u bse q ue nt treat me nt patter ns a n d treat me nt d urati o n after e n d ocri ne t hera p y a m o n g 
a d va nce d metastatic breast ca ncer fe male pati e nts t o a d dress treat me nt para di g m c ha n ges 
i n Ja pa n wit h t he la u nc h of ne w treat me nt o pti o n. F or t he a d va nce d metastatic breast 
ca ncer male patie nts, t he a nalys is will be e x pl orat or y . Detaile d met h o d ol o g y  f or 
s u m mar y a n d statistical a nal yses of data c ollecte d i n t his stu d y  will be d oc u me nte d i n a 
statistical anal ys is pla n ( S A P), w hic h will be date d, file d a n d mai ntai ne d b y t he s p o ns or.  
T he S A P ma y  m o dif y t he pla ns o utli ne d i n t he pr ot oc ol; a n y maj or m o dificati o ns of 
pri mar y  e n d p oi nt defi niti o ns or t heir a nal ys es w o ul d be reflecte d i n a pr ot oc ol 
a me n d me nt.

M ilest ones :
C o m p letio n of feasi bilit y  assess me nt
1 0 Dec e m ber 2 0 1 8 ( D o ne )
Start of data c ollecti o n 
A pr il 2 0 0 8 ( Alrea d y starte d b y Me dical Data Visi o n C o., L t d.)
E n d of data c ollecti o n 
3 1 Oct o ber 2 0 2 2
Fi na l st u d y re p ort
N o ve m ber 2 0 2 3
5. A M E N D M E N T S A N D U P D A T E S
A me n d m e nt 
n u m ber
D ate
Pr ot oc ol secti o n(s) 
c h a n ge d
S u m m ar y of a me n d me nt(s)
Re as o n
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 8 of 2 5
1
2 7 Marc h 2 0 1 9
A N N E X 1. 
A p pe n di x 1
Re place A p pe n di x 1
D ue t o fi nalizati o n of S A P 
2
0 1 D ece m ber 2 0 1 9
Se cti o n 3, 4, 5, 8, 9
A p pe n di x 1 , i ncl u de d 
“ ot her ca ncer t y pe” i n 
e xcl usi o n criteria of 
t he al g orit h m
C ha n ge NI  st u d y lea d,
A d d t he o bjecti v e,
A d d t he varia ble
D ue 
t o c o nsi derati o n 
t he 
pr ot oc ol u p date base d o n t he 
first data a nal ysis res ult
3
3 1 Marc h 2 0 2 1
Secti o n 8 - 9
A d d iti o n of o bjecti ves t o re veal 
t he de m o gra p hic
a n d cli nical 
c haracteristics of A B C patie nts 
a n d to a n al yze e n d ocri ne base d 
t hera p y f or A B C patie nts
T o 
descri be
treat me nt 
para di g m c ha n ges wit h 
t he 
la u nc h of 
ne w 
treat me nt 
o pti o n, C D K 4/ 6 i n hi bit or.
Sect i o n 8- 9
Re vise t he descri pti o n t o clarif y 
t he o bjecti ves
T o clari f y t he o bjecti ves b y
acc urate descri pti o n.
Se cti o n 7
A d diti o n of bac k gr o u n d of ne w 
o bjecti ves
Re vis i o n of t he descri pti o n
T o e xplai n
t he reas o n of 
o bjecti ves 
a d de d 
at 
a me n d me nt .
T o clari fy t he bac k g r o u n d b y
acc urate descri pti o n.
Sect i o n 
9. 2 . 1, 
A p pe n di x 1
A d diti o n t o I ncl usi o n criteria.
# 3
Dia g n osis 
of 
sec o n dar y 
mali g na nt ne o plas m base d o n 
I C D-1 0 ( C 7 7. x, C 7 8. x, C 7 9. x)
T o 
excl u de 
a dj u va nt 
e n d ocri ne 
t hera p y 
clearl y 
fr o m e n d ocri n e t hera p y for 
metastatic 
setti n g o wi n g
t o 
t he a d diti o n of t he o bjec ti ves
Secti o n 9. 3. Varia bl es
A d diti o n of Varia bles
T o descri be t he d urati o n of 
e n d ocri ne t hera p y base d o n 
t he a d diti o n of o bjecti ves
S ecti o n 
9. 4 
Data 
s o urces
A d diti o n of t he descri pti o n.
T o 
descri be 
data 
s o urces 
m ore acc uratel y.
Secti o n 4, 6 a n d Ta ble 
1
C ha n ge 
milest o nes 
a nd data 
peri o d
T o f oll o w-u p t he st u d y f or 
l o n ger-ter m.
S ecti o n 2
A d diti o n of a b bre viati o ns.
D ue 
t o t he 
ad diti o n 
of 
o bjecti ves 
f or 
t he 
a me n d me nt.
A p pe n di x 2
A d diti o n of c o m p o u n ds
T o 
a d d 
ne wl y 
a p pr o ve d 
c o m p o u n ds
Secti o n 3
C ha n ge NI  st u d y c o-lea d
6.
M I LE S T O N E S
Milest o ne
Pl a n ne d d ate
C o m plet i o n of feasi bilit y assess me nt
1 0 Dec e m b er 2 0 1 8 ( D one)
Star t of data c ollecti o n 
A pr il 2 0 0 8 ( Alrea d y starte d b y Me dical Data Vi si o n C o., Lt d. )
E n d of data c ollecti o n
3 1 Oct o ber 2 0 2 2
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 9 of 2 5
Fi nal st u d y re p ort
N o ve m ber 2 0 2 3
7. R A TI O N A L E A N D B A C K G R O U N D
Breast ca ncer is t he m ost c o m m o n ca ncer i n w o me n in Ja pa n , wi t h nearly 7 4 ,0 0 0 ne w cases 
dia g n ose d i n 2 0 1 2 a n d t he i nci de nce rate has stea dil y i ncrease d. In 2 0 1 4, t here are o ver 
1 0 ,0 0 0 deat hs as breast ca ncer patie nts 1.  Breast ca ncer pre va le nce rate of Ja pa nese w o me n 
b y  a ge gr o u p be ga n t o i ncrease fr o m t he 3 0s, pea k e d i n t he latter half of t he 4 0s, after t h at it 
re mai ne d al m o st c o nsta nt, a n d gra d ually dec rease d fr o m t he late si xties2.
W he n t he metastasis is see n at t he first dia g nosis (a b o u t 6 % of breast ca ncer patie nts), t he 
pr o g n osis is re mar ka b ly p o or a n d t he 5 -ye ar s ur vi val rate dr o ps t o 2 6. 3 % 3. I n a d diti o n, e ve n 
if metastasis is n ot see n at t he ti me o f i nitial dia g n osis, it is esti mate d t hat a b o ut 2 0% t o 3 0 % 
of patie nts will h a ve metastasis / rec urre nce after ra dical treat me nt f or t he pri mar y tu m or 4.
A cc ordi n g t o T he Ja pa nese Breast Ca ncer S ociet y Cli nic al Practice G ui delines f or Breast 
Ca ncer 2 0 1 8 2, the o bjecti ves f or metastatic/ rec urre nt breast ca ncer are (1) T he pr ol o n gati o n
of s ur vi v al a nd ( 2) T he i m pr o ve m e nt/ mai nte na nce of t he q ualit y of li fe.
A p pr o xi m atel y tw o -t hir ds of breast ca ncers are h or m o n e re ce pt or p ositi ve ( H R +) 5.  
E n d ocri ne t hera p y is t he mai n sta y of treat me nt f or patie nts wit h H R + disease .  T he first-li ne 
en d ocri ne treat me nt f or H R +/ H E R 2 - a d va nce d breast ca nce r ty picall y i ncl u des ar o matase 
i n hibit ors (e. g. a nastr oz ole, letr oz ole, or e xe mesta ne) an d estr o ge n rece pt o r a nta g o nists (e. g.
ta m o xife n or f ul vestra nt)2. T he c h oice of pri mar y  e n d ocri ne t hera py f o r pat ie nts wit h 
H R +/ H E R 2- a d va nce d breast ca ncer is ofte n base d o n se veral c o nsi derati o ns i ncl u di n g pri or
use of p ost o perati ve a dj u va nt e n d ocri ne t hera p y, p ote nt ial si de effects, pr o gres si o n free 
pe ri o d of pret reat me nt dr u gs , a n d me n o pa usal stat us of patie nts .
Pal b oc icli b is a n oral, c ycli n-de pe n de n t ki nase ( C D K) 4/ 6 i n hi bit or, w hic h pre ve nts 
de o x yri b o n ucleic aci d ( D N A) re plicati o n b y pr o hi biti n g pr o gressi o n fr o m G 1 t o S p hase 
d uri n g cel l di visi o n, t here b y pre ve nti n g t u m or cell pr oliferati o n t hr o u g h ce ll c ycle c o ntr ol.
T he cli nical st u dies i n w hic h H R +/ H E R 2 - a d va nce d or metastatic breast ca ncer were 
c on d ucte d i n c o m bi nati o n wit h e n d ocri ne t her a p y.  T he P AL O M A - 2 st u d y (t he gl o bal p hase
3 ) s h o we d t hat pr ogressi o n -free s ur vi val ( P F S) was i m pr o ve d w it h pal b ocicli b pl us letroz ole
c o m pare d t o place b o pl us letr oz ole i n t he treat me nt of p ost me n o pa usal w o me n wit h estr o g e n 
rece ptor (E R )+/ H E R 2 - a d va nce d breast ca ncer i n t he first-li ne setti n g. M e dia n P F S [ 9 5 %
C o nfi de nce i nter val (CI )] was 2 4. 8 [ 2 2. 1- n ot esti mate (N E) ] m o nt h s f or pal b ocicli b pl us 
letr oz ole, a n d 1 4. 5 ( 1 2. 9-1 7. 1) m o nt hs f or place b o pl us letr oz ole 6. In t he P A L O M A -3 st u d y
(t he gl o bal p hase 3), t he c o m bi nati o n of pal b ociclib a n d f ul vestra nt w as ass ociate d wit h 
si g nifica nt i m pr o ve me nts i n P F S c o m pare d wit h f ul vestra nt pl us place b o i n patie nts wit h 
E R +/ H E R 2 - a d va nce d breast ca ncer as t he sec o n d or later t ha n sec o n d treat me nt [t he media n 
P F S ( 9 5 % CI ) was 1 1. 2 ( 9. 5-1 2. 9) m o nt hs f or pal b ocicli b pl u s f ul vestra nt, a n d 4. 6 ( 3. 5 - 5. 6) 
m o nt hs f or place b o pl us letr oz ole ]. A d diti o nall y b ot h pre -me n o pa usal a n d p ost -me n o pa usal 
patie nts were i ncl u de d i n t he P A L O M A -3 st u d y  a n d t he efficac y of pal b o cicli b treat me nt was 
o bs er ve d re gar dless of the me n o pa usal stat u s7, 8, 9. A n ot her st u d y, A 5 4 8 1 0 1 0 st u d y  (Ja pa n 
p hase 2) was c o n d ucte d i n Ja pa n a n d t he 1-year disease free s ur vi val rate ( 9 0 % CI ) t hat was 
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 0 of 2 5
t he pri mar y e n d p oi nt f or t he st u d y was 7 5. 0 % ( 6 1. 3- 8 4. 4). The P F S, o ne of t he sec on dar y  
e n d p oi nts di d n ot reac h t he me dia n ( 9 5 % CI was 1 6. 7 m o nt hs to N E) 1 0.
Pal b ocicli b is t he first C D K 4/ 6 i n hi bit o r a p pr o ve d i n Ja pa n i n c o m bi nati o n wit h e n d ocri ne 
t hera py f or treat me nt of H R +/ H E R 2- a d va nce d b reast ca ncer. Palb oc icli b was a p pr o ve d i n
Se pt e m ber 2 0 1 7 a n d la u nc he d in Dece m ber 2 0 1 7. I n t he Ja pa nese pac ka ge i nsert f or 
pal b ocicli b, t he data f or o nl y 5 9 Ja pan ese patie nts w h o were a d mi nistrate d pal b ocicli b i n 
P A L O M A -2 a n d P A L O M A -3 st u dies is descri be d . Als o nei t her treat me nt li ne n or 
c o nc o mita nt treat me nt dr u g is defi ne d i n t he Ja pa nese pac ka ge i nsert a n d t here is n o data f or 
treat me nt se q ue nce of pal b ocicli b. T heref ore, real w orl d data f or pal b ocicli b is nee de d t o
clarif y t he treat me nt patter n of pa l b ocicli b i n Ja pa n. T his st u d y  ai ms t o descri be patie nt 
de m o gra p hi c, treat me nt patter ns a n d treat me nt d urati o n a m o n g H R +/ H ER 2 - a d va nce d breast 
ca ncer ( A BC) pati e nts w h o i nitiate d pal b ocicli b . I n a d diti on, t h is st u d y will descri be 
s u bse q ue nt treat me nt patter ns a n d treat ment d urati o n after pal b ocicli b-base d t hera py.  I n 
a dditi o n, t h is st u d y will descri be h o w treat me nt para di g m c ha n ges wit h t he la u nc h of ne w 
treat ment o p ti o n, C D K 4/ 6 i n hi bit or. R ec o m me n dati o ns a n d usa ge of treat me nts var y  bet wee n 
c o u ntries acc or di n g t o t he a p pr o val a n d a vaila bilit y of i n di vi d ual a ge nts . E n d ocri ne treat me nt 
has l o n g bee n rec o m me n de d o ver c he m ot hera p y f or s yste mic t hera p y. I n t he Ja pa nese Breast 
Ca ncer S ociet y Cli nical Practice g ui d eli nes f or Breast Ca ncer 2 0 1 8, ar o matase i n hi bit or( AI)
m o n ot hera p y, c o mbi nati o n of AI a n d C D K 4 / 6 i n hi bit or, a n d f ulvestr a nt m o n ot hera p y ha d
bee n rec o m me n de d wit h t he sa me rec o m me n dati o n le vel f or i nitial treat me nt of 
p ost me n o p a usal H R + H E R 2 - A B C. I n 2 0 2 0, t he rec o m me n dati o n le vel was rec o nsi dere d a n d 
c o m bi nati o n of AI a n d C D K 4/ 6 i n hi bit or is m ost str o n gly rec o m me n de d in t he g ui deli ne. B ut
there is li mite d i nf or mati o n o n t he real-w orl d use a n d treat me nt o utc o m e of t h ese e n d ocri ne 
base d t hera pies i n Ja pa n. As t he a d diti o nal objecti ves , t his st u d y ai ms t o descr i be patie nt 
de m o gra p hic, treat me nt patter ns a n d treat me nt d urati o n a m o n g H R +/ H E R 2 - A B C patie nts 
w h o i nitiate d e n d ocri ne base d t hera p y f or a d va nce d/ metastat ic setti n g.
8. R E S E A R C H Q U E S TI O N A N D O B J E C TI V E S
T he p ri mar y o bjecti ve of t his st u d y  is t o descri be patient de m o gra p hics , treat me nt patter ns 
a n d treat me nt d urati o n of pal b ocicli b , a n d su bse q ue nt treat me nt p atter ns a n d treat me nt 
d urati o n after pal b ocicli b -base d t hera py a m o n g a d va nce d metastatic breast ca ncer fe male 
patie nts i n Ja pa n i nitiati ng treat m e nt wit h pal b ocicli b f oll o wi n g dr u g la unc h i n Ja pa n ( 1 5 
Dec e m ber 2 0 1 7 ). T he sec o n dar y o bjecti ve of t he st u d y is t o descri be patie nt de m o gra p hics, 
treat me nt patter ns of A B C patie nts a n d treat me nt d urati o n of e nd ocri n e thera p y , a n d 
s u bse q ue nt treat me nt patter ns a n d treat me nt d urati o n after e n d ocri ne t hera p y a m o n g 
a d va nce d metastatic breast ca ncer fe male patie nts t o ad dress treat me nt para di g m c ha n ges i n 
Ja pa n wit h t he la u nc h of ne w treat me nt o pti o n . F or t he a d va nce d m etastatic breast ca ncer 
male patie nts, t he a nal ys is will be c o n d uc te d e x pl orat or y beca use male patie nts are e xtre mel y 
rare a n d t he y were n ot i ncl u de d in cli nical st u dies. M ore s pecificall y, Me dical Data Vis i o n 
(M D V ) data base will be utilize d t o ac hie ve t h e f oll o wi n g researc h o bjecti ves:
1.
T o c haracterize t he de m o gra p hic a n d cli nical c hara cteristics of A B C patie nts at t he 
i nitiati o n of treat me nt wit h pal b ocicli b
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 1 of 2 5
2.
T o d escri be t he treat me nt patter ns of pal b ociclib, i ncl u di n g li ne of t hera py a n d t ype of 
e n docri n e t hera p y c o m bi ne d wit h pal b ocicli b, a n d i nitial d osa ge
3.
T o e val uat e ti me t o treat me nt fail ure ( T TF ) of pa l b ocicli b i n c o m bi nati o n wit h 
e n d ocri ne t hera py b y  t he li ne of t hera py
4.
T o descri be t he treat me nt pat ter ns of s u bse q ue nt t hera py afte r e n d of pal b ocic li b
treat me nt, i ncl u di n g li ne of t hera p y a n d t ype of treat me nt
5.
T o e val uate T T F of s u bse q ue nt t hera py after e n d of pal b ocicli b treat me nt
6.
T o descri be c ha n ges i n treat me nt patter n bef ore a n d after t he la u n ch of pal b ocicli b ,
t he re visi o n of cli nical gui deli ne i n Ja pa n.
7.
T o d escri be t he use of a nti bi otics a n d/ or G-C S F d u ri n g treat me nt wit h pal b o cicli b
8.
T o descri be t he fre q ue n c y of bl o o d tests d uri n g tre at me nt wit h pal b o cicli b
9.
T o c hara cterize t he de m o gra p hic a n d cli nical c haract eristics of A B C patie nts at t he 
i nitiati o n of treat me nt f or A B C
1 0. T o descri be t he treat me nt patter ns of eac h li ne of t hera p y f or A B C patie nts
1 1. T o e v al uate T T F of e n d ocri ne t hera p y  f or A B C patie nts
1 2. T o descri be t h e treat me nt patter ns of s u bse q ue nt t hera py after en d of e n d ocri ne 
t hera py f or A B C patie nts, i ncl u di n g li ne of t hera p y a n d ty p e of treat me nt
1 3. T o e val uate T T F of s u bse q ue nt t hera py after en d of e n d ocri ne t hera p y f or A B C
patie nts
1 4. T o descri be t he u se of a nti bi otics a n d/ or G- C S F d ur i n g treat me nt wit h e n d ocri n e 
t hera py f or A B C
9. R E S E A R C H M E T H O D S 
9. 1. St u d y d esi g n
T hi s is a retr os pecti ve o bser vati o nal st ud y  f oc usi n g o n patie nts di a g n ose d wit h breas t ca ncer
i n Ja pa n usi n g de -i de ntifie d clai m data fr o m M D V data base . P atie nts w h o meet t h e i ncl usi o n 
criteria will be retros pecti vel y  selecte d fr o m M D V
data base. T h e al g orit h m t o defi ne t he first 
li ne treat ment f or a d va nce d breast ca nce r is descri be d in a p pen di x 1.
9. 2. Setti n g
Ja pa nese patie nt s dia g n ose d wit h breast ca nc er a n d w h ose data wer e e ntere d i nt o M D V 
data base fr o m A pril 2 0 0 8 will be i ncl u de d i n t his st u d y. M D V data wil l be e xtracte d f or eac h 
patie n t fr o m t he first data t o f oll o wi n g data peri od ( Ta ble 1 ). 
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 2 of 2 5
T a ble 1 D at a pe rio d
A n al ysis ye ar
D at a peri o d
First Year
A pril 2 0 0 8 t o Dec e m ber 2 0 1 8
Sec o n d Year
A p ril 2 0 0 8 t o A u g ust 2 0 1 9
T hi r d Year
A pril 2 0 0 8 t o Dec e m ber 2 0 2 0
F o urt h Y ear
A p ril 2 0 0 8 t o Oct o ber 2 0 2 1
Fift h Y ear
A pr il 2 0 0 8 t o Oct o ber 2 0 2 2
Patie nts meeti n g all o f t he f oll o wi n g criteria will be selected f or a nal ys is.
9. 2. 1. I ncl usi o n criteri a
Patie nts w h ose data were e ntere d i n t o M DV data base fr o m A pril 2 0 0 8 will be i ncl u de d a n d
m u st meet all of t he f oll o wi n g i ncl usi o n crit eria t o be eli gi ble f or i ncl usi o n i n t he st u dy:
1.
Di a g n osis of breast ca ncer base d o n I nter nati o nal statistical classificati o n of d iseases a n d
relate d h ealt h p r o ble ms 1 0 t h re visi o n (I CD- 1 0) ( C 5 0. x x );
2.
Recei v ed at l e ast o ne prescri pti o n of e n d ocri ne t h era p y d r u gs d uri n g t he i n de x peri o d
( See A p pe n di x 2).
3.
D iag n osis of sec o n dar y  mali g na nt ne o plas m base d o n I C D - 1 0 ( C 7 7. x, C 7 8 . x, C 7 9. x)
9. 2. 2. E xcl usi o n criteri a
P atie nts me eti n g a n y of t he f oll o wi n g criteria will n ot be i ncl u de d i n t he st u d y:
1.
Recei ve d at least o ne prescr i pti on of a nti-H E R 2 t h era p y ( Trast uz u ma b , Tr astu z uma b 
e mta nsi ne, Pert uz u ma b , a n d La pati n i b t osilate hy drate : see A p pe n di x 2 ) d uri n g t he i n de x 
peri o d.
9. 3. V ari a b les
T he varia bles are descri be d i n t he f oll o wi n g t a ble. T he det aile d defi niti o ns are i ncl u de d i n t he
S A P . 
T a ble 2 V ari a ble s
V ari a ble
R ole
D at a s o urce(s)
O per ati o n a l defi niti o n
A ge
B aseli ne 
c haracteristic
At date of prescri pti o n f or first li ne 
treat me nt f or a d va nce d breast ca ncer
At pal b oci clib t reat me nt i nitiati o n
Str uct u re d data fiel d
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 3 of 2 5
Ge n der
B a seli ne 
c har acteristic
At da te of prescri pti o n f or first li ne 
treat me nt f or a d va nce d breast ca ncer
At pal b ocicli b treat me nt i nitiati o n
Str uct ure d data fiel d
Wei g ht
B aseli ne 
c haracteri stic
A t pal b ocicli b treat me nt i nitiati o n
O nl y i n patie nt
Str uct ure d data fiel d
Hei g ht
B aseli ne 
c haracter istic
At date of prescri pti o n f or first li ne 
treat me nt f or a d va nce d breast ca ncer
O nl y i n patie nt
St r uct ure d data fiel d
Pal b ocicli b treat me nt 
date
e xp os ure
Date of eac h prescri pti o n or der f or 
pal b ocicli b
Str uct ure d data f iel d
Pal b ocicli b dail y d o se
e x p os ure
At eac h pre scri pti o n or der
Str uc t ure d data fiel d
Pal b ocicli b treat me nt 
d urati o n
e xp os ure
D urati o n fr o m first prescri pti o n t o 
last prescri pti o n f or pal bocicli b
Str uct ure d data fiel d
E n d ocri ne t hera p y
c o m bi ne d wit h 
pal b ocicli b
e xp os ure
E n d o cri ne t hera p y prescri be d wit h 
pal b ocicli b
See A p pe n di x 2
Treat me nt patter n of 
eac h li nes of t hera p y
e x p os ure
A t eac h prescri pti o n or der
See A p pe n di x 2
C he m ot her ap y  
treatme n t patter n
e x p os ure
S tart a n d e n d date of eac h 
or der/ p rescripti o n , dr u g na me f or 
c he m ot hera p y dr u gs
See A p pe n d i x 2
E n d ocri ne t herap y  
treat me nt patter n
e x p os ure
S tart a n d e n d date o f eac h 
or der/ prescri pti o n , dr u g na me f or 
en d ocri ne t hera p y dr u gs
See A p pe n di x 2
E n d ocri ne t hera p y 
treat me nt d urati o n
e x p os ure
D urat i o n fr o m first prescri pti o n t o 
last prescri pti o n f or e n d ocri ne
t hera p y dr ugs
See A p pe n di x 2
T i me t o treat me nt 
fail ure
ex p os ure
Ti m e t o treat me nt fail ure is defi ne d 
as t he ti me fr o m  t he start date of 
treat me nt t o e n d date of t reat me nt. 
Ti m e to t reat me nt fail ure will be 
ce ns ore d at patie nt dise nr oll me nt or 
e n d of st u d y peri o d
Str uct ure d data fiel d
G- C S F treat me nt date
e x p os ur e
Date of eac h or der / prescri pti o n 
Base d o n A T C c o de 
“L 0 3 A 1 ”
A nti bi otics treat me nt 
da te
e x p os ure
Date o f eac h or der/ prescripti o n 
Bas ed o n A T C c o de “J 0 1”
a n d “J 0 2”
D urati o n o f t he a dj u va nt
t hera p y
e x p os ure
Date o f eac h or der/ prescri pti o n 
See t he S A P
D urati o n fr o m s ur ger y
t o t he starti n g of 1st li ne 
t hera p y
e x p os ure
Date of eac h or der/ p rescri pti o n 
See the S A P
B l o o d test d ate
ex p os u re
Date of eac h or der
Se e t he S A P
9. 4. D at a s ources
M D V Data base i n base d o n healt h clai ms data a n d a d mi nistrati ve data or Dia g n osis 
Pr oce d ure C o m b i nati o n (D P C ) data fr o m o ver 36 0 J apa nese ac ute h os pitals.
T he d ata base is releas e d a n d mai ntai ne d b y Me dical
Da ta Visi o n I nc. , Lt d. T he data 
c o ntai ne d i n t he data base i ncl u des a n o n ymize d patie nt i de ntifier, a ge, ge n der, dia g n osis
b ase d o n I C D c o de, me dical pr oce d ures, pr escri pti o ns, i n patie nt/ o ut patie nt stat us, a n d 
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 4 of 2 5
la b orat or y data. T h e data base d oes n ot i ncl u de i nf or mati o n a b o ut treat me nt o utc o me s or 
details of dia g n osis . T he data are u pdate d m o nt hl y. Dat a c ollecte d fr o m A pril 2 0 0 8 will be 
us e d i n this st u d y .
9. 5. St u d y size
T his is a descri ptiv e st u d y a n d sa m ple size a n d p o wer calc ulati o ns are n ot a p plicable .  All 
eli gi ble patie nts wit h breas t ca ncer dia g n osis a n d w h o recei ve d e n d ocri ne t her a p y dr u gs a n d 
w h o d i d n’t receive a nti -H E R 2 t he ra py dr u gs ( defi ned as H R +/ H E R 2 - breast ca ncer) will be 
i ncl ude d i n t he a nal ys is. Acc or di n g t o a preli mi nar y feasi bilit y assess me nt, t he n u m ber of 
H R +/ H E R 2 - breast cancer patie nts is 1 0, 3 1 2 4 .
9. 6. D at a m a n a ge me nt 
T his is a retr os pect i ve a n d n o n-i nter ve nti o nal st u d y usi n g t he Me dical Data Visi o n I nc 
(M D V ) data base w h os e data c ollecti o n is c o ntr olle d b y M D V. I n t his st u d y, Pfizer will
re q uest data e xtracti o n base d o n incl usi o n/e xcl usi o n criteria t o M D V, a n d C S S a n d Pf izer 
will use t he dataset w hic h is q ualit y  c o ntr ol (Q C )’ d b y  M D V f or a nalys is.
Patie nt data are pr o vi de d b y
M D V . I nitial assess me nts will be ma de usi n g descri pti ve 
statistics a n d data vis ualizati o n: hist o gr a ms, b ar c harts, a n d b o x pl ots of varia bles. 
Reas o na ble t hres h ol ds wi ll be set t o i de ntif y e xtreme o utliers (e. g. 1. 5 * i nter q uartile ra n ge).
Ass u m pti o ns o f n or mal distri b uti o ns of t he a nal ysis varia bles will be e val ua te d. All data 
ma na ge me nt a n d statistic al a nal yses will be c o n d ucte d usi n g Statistical A nal ysis S oft ware 
( S AS v. 9. 4) a n d R versi o n 3. 4 . 0 or later ( T he R F o u n dati o n f or Statistical C o m p uti n g). 
F u rt her details re gar di n g data ma na ge me nt will be state d i n a S A P.
9. 7. D at a a n al ysis 
T he pri mar y o bjecti v e of this st u d y  is t o descri be patie nt de m o gra p hics, treat me nt patterns 
a n d treat me nt d urati o n o f pal b ocicli b, a n d su bse q ue nt treat me nt patter ns a n d treat me nt 
d urati o n after pal b ocicli b -base d t hera p y a m o n g t he a d va nce d me tastatic br east ca ncer fe male 
patie nts i n Ja pa n i nitiati n g treat me nt wit h pal b ocicli b f oll o wi n g dr u g la unc h i n Ja pan.  F or 
t he a d vance d metast atic br east ca ncer male patie nts , t he a nal ysis will be e x pl orat or y .
Detaile d met h o d ol o g y f or s u m mar y  a n d statistical a nal ys es of data c ollecte d i n t h is stu d y  will 
be d oc u me nte d i n a S A P, w hic h will b e date d, file d a n d mai ntai ne d b y  t he s p o ns or. T he S A P 
ma y m o dif y t he pla ns o utli ne d i n t he pr ot oc ol; a n y m ajor m o dificati o ns of pri mar y  e n d p oi nt 
defi n iti o ns or t heir anal yses w o ul d be reflecte d i n a pr ot oc ol a me n d me nt.
9. 7. 1. St atistic al met h o ds
Descri pti ve stat istics will be re p orte d f or c onti n u o us varia bl es usi n g mea n, stan dar d de viati o n, 
mi ni m u m, 1 st q uartile, me dian, 3r d q uartile, a n d ma xi m u m. Cate g orical varia bles will b e 
re p orte d usi n g fre q ue ncies a n d pr o p o rtio n s. 
Missi n g val ues will als o be re p orte d f or eac h 
varia ble. F or pr o p orti o n s, 9 5 % c o nfi de nce i nter vals will b e pr o vi de d usi n g Wils o n sc o re 
met h o d w he n a p pr o priate. 
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 5 of 2 5
Detaile d met h o d ol o g y  f or s u m mary a n d statistical a nal ys es of d ata c ollecte d i n t his stu d y wi ll 
be d oc u me nte d i n t he S A P, w hic h will be d ate d, file d a n d mai ntai ne d b y t he s p o ns or. T he
S A P ma y  m odif y  t he pla ns o utli ne d i n t he pr o t oc ol; a n y majo r mo dificati o ns of pri mar y  
e n d p oi nt defi niti o ns or t heir a nal y ses w o ul d be r eflecte d i n a pr ot oc ol a me n d me nt.
9. 7. 1. 1. O bjecti ve s
9. 7. 1. 1. 1. Tre at me nt p atter n a n d t ar get p o p ul ati o n of p al b o cicli b
De m o gra p hic a n d cli n ical c haracteristics (as liste d i n secti o n 9. 3 i n Ta ble 2) wi ll be 
descri pti vel y s u m marize d f or all pati e nts i nitiati n g pal b ocicli b a n d will be e x pl ore d b y  li ne of
t hera p y ( pr o vi de d data are s ufficie nt) .
T reat me nt patter n of pal b ocicli b wil l be assesse d base d o n t he perce nt a ge of patie nts
i nitiati n g pal b ocicli b line, as first -li ne, sec o n d-li ne, a n d s o o n. S pecificall y, t he n u m be r of 
patie n ts i nitiati n g pal b ociclib l i ne (e. g. first-li ne, sec o n d-li ne) di vi de d b y  the t otal n u m ber of
patie nts i n itiati n g a ny ca ncer treat me nt li ne (as first-li ne, sec o n d-li ne, a n d s o o n, 
res pecti vel y) will be calc ulate d . M ore o ver, t he distri b uti o n of eac h e n d ocri ne treat me nt 
c o m bi nati o n wit h p al b ocicli b li ne, as perce nta ges, will be assesse d.
9. 7. 1. 1. 2. T i me t o tre at me nt f ail ure of p al b ocicl i b i n c o m bi nati o n w it h e n d ocri ne 
t her a p y
Ti me t o treat me nt fail ure of pal b ocicli b i n c o m bi nati o n wit h e n docri ne t hera p y is def i ne d as 
ti me fr o m t he date of first pa l bo cicli b prescri pti o n t o t he t o t he date of last pal b ocicli b 
prescri pti o n or t o t he date of t he ne xt li ne of t hera p y ( descri be d in t he S A P) , defi ne d as t he 
e n d of pal b o ciclib treat me nt. D ur ati o n will be calc ulate d i n da y s a nd descri pti vel y  
s u m marize d. Als o, Ka pla n -Meier a na l ysis will be perf or me d t o a nal yze ti me t o treat me nt 
fail ure, a n d Ka pla n -M e ier c ur ves will be prese nte d. F or t h is p ur p ose, ti me t o treat ment 
fail ure will be ce ns ore d a t t he earliest of a n y of t he f oll o wi n g: latest patie nt rec or d, or t he e n d 
of t he st u d y  peri od. Re gar di n g ce ns ori n g, d etails will be s peci fie d i n t he S A P. A nal y sis will
be str atifie d b y t he treat me nt li ne p ositi o n (e.g. first-li ne, sec o n d-li ne).
9. 7. 1. 1. 3. Tre at me nt p atter n of s ubse q ue nt t her a p y after p al b ocicli b , i ncl u di n g li ne of
t her a p y a n d t y pe of tre at me nt
F or t he fir st treat ment li ne wit h pal b oci cli b, t he pr o p orti o n of eac h a nti -ca n cer dr u g i n t he 
s u bse q ue nt t hera py after p alb ocicli b wi ll be calc ulat e d, as t he n u m ber of patie nts ha vi n g t he 
c orres p o n di n g a nti-ca ncer dr u g i n the s u bse q ue nt t hera py di vi de d b y  t he t otal nu m ber of 
p atie nts wit h a s u bse q ue nt t hera p y after pal b oci clib li ne . M ore o ver, t he pr o p o rti o n of eac h 
treat me nt li ne re gi me n (i ncl u di n g a nti-ca ncer dr u g cate g o r y c o m bi nati o ns) will be calculate d 
i n a si milar ma n ner. A d diti o nall y, t he sa me an a lys is will be perf or me d a fter stratificati o n b y 
t he p ositi o n of pal b oci cli b li ne (e. g. first-li ne, seco n d -li ne), w he n p ossi ble. D etails will be
desc ri bed i n t he S A P.
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 6 of 2 5
9. 7. 1. 1. 4. T i me t o tre at me nt f ail ure of s u bse q u e nt t her a p y after p al b ocicli b
T i me t o treat me nt failure of s u bse q ue nt t hera p y  after pal b ocicli b is defi ne d as ti me fr om t he 
d ate of first ne xt li ne of t hera p y  after e n d of pal b ocicli b treatme nt t o t he date o f l ost t o 
f oll o w-u p or t o t he date of t he sec o n d ne x t li ne of t hera py. D urati o n will be calc ulate d i n
da y s an d descri pti vel y  s u mmari ze d. Als o, Ka pla n -Meier a nal y sis will be perfor me d t o 
a nal yz e ti me t o trea t ment fail ure , an d Ka pla n -Meie r c ur ves will be pres ente d. F or t his 
p ur p ose, ti me t o treat me nt fail ure will be ce ns ore d at t he earliest of a n y  of t he f oll o wi ng : 
latest patie nt recor d, or t he e n d of t he st u d y peri o d. Re gar di n g ce nsori n g, deta ils will be
s pecified i n t h e S A P.
9. 7. 1. 1. 5. C h a n g es i n tre at me nt p atter n (e. g. b ef ore vs. after t he l a u nc h, a n n u al re vie w 
after l a u nc h of p al b ocicli b )
Wit h i n eac h s pecific ti me i nter vals ( Ti me i nter val defi niti o n will be a d dresse d i n t he S A P), 
f or eac h t hera py , t he pr o p orti o n of pati e nts i nitiati n g t he c orres p o n di n g t hera py (as first-li ne, 
sec o n d-li ne, a nd s o o n) , defi ne d as t he n u m ber of patie nts i nitiati n g t he c orres p o n di n g 
t hera py (as first-li ne, sec o n d-li ne, a n d s o o n) di vi de d b y  t he t otal n u m ber of patie n ts i nitiatin g 
a n y ca ncer treat me nt li ne (as first-li ne, sec o n d-li ne, a n d s o o n, res pecti vel y). Res ults will be 
gra p hic all y dis pla y e d usi n g bar p l ots.
9. 7. 1. 1. 6. Us e o f a nti bi otics a n d/ or G-C S F after a d mi nistr ati o n of p al b ocicli b
T he p r o p orti o n of patie nts presc ri be d a nti bi otics a n d t he pr o p orti o n of patie nts pr escribe d G -
C S F d uri n g treat me nt wit h pal b ocicli b wi ll be calc ulate d as t he n u m ber of patie nts prescri be d 
t he c orres p o n di n g treat me n t di vi de d b y  t he t otal n um ber of patie nt s prescri be d pal b ocicli b.
9. 7. 1. 1. 7. Fre q ue nc y of Bl o o d Test
T he fre q ue nc y of bl o o d test after a d mi nistrati o n of pal b ocicli b will be calc ulate d as t he 
n u m ber of patie nts prescri be d t h e c orres p o n di n g tr eatme nt di vi de d b y  t he t otal nu m ber of 
patie nts pre scri be d pal b ocicli b.
9. 7. 1. 1. 8. Tr e at me nt p atter n a n d t a r get p o p u l ati o n of e ac h li ne of t her a p y f or A B C
De m o gr a phic s a n d cli nical c haracteristics (as liste d i n secti on 9. 3 i n Ta ble 2 ) will be 
descri pti vel y s u m marize d f or patie nts i nitiati n g e n docri ne t hera p y a n d will be e x pl ore d b y  
line of t hera p y wit hi n eac h ti me i nter val, in w hic h eac h t hera p y starte d (t he tim e i nter vals 
will be defi ne d i n t he S A P).
Li ne of t hera p y will be defi ne d base d o n t he dr u gs descri be d i n 
a p pe n di x 2 .
T reat me nt patter n of e n d ocri ne t hera p y wi ll be assesse d based o n t he perce nta ge of p atie nts 
i nitiati ng e n d ocri ne t hera p y, as first-li ne, seco n d-li ne, a n d s o o n. S pecificall y , t he n u m ber of
p atie nts i nitiati n g en d ocri ne t hera p y ( e. g. first-li ne, sec o n d-li ne) di vi de d by t he t otal n u m ber 
of patie nts i nitiati n g a ny can cer treat me nt li ne (as first-li ne, sec o n d-li ne, a n d s o o n, 
res pecti vely) will be c alc ulate d.
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 7 of 2 5
9. 7. 1. 1. 9. T i me t o tre at me nt f ail ure of e n d ocri n e t her a p y
Ti me t o treat me nt fail ure of e n d ocri ne t hera p y is defi ne d as t he ti me fr o m t he date of first 
pres cri pti o n of e n d ocri ne t hera p y t o t he date o f last e nd ocri ne prescri pti o n or t o date of t he 
ne xt li ne of t hera p y , defi ne d as t he e n d of t he t hera p y. De scri pti ve s u m mar y f or t he ti me t o 
treat me nt fail ure will be calc ulate d usi n g Ka pla n -Meier met h o d a n d Ka pla n -Me ier c ur ves 
wil l be als o prese nte d. T i m e t o treatme nt fail ure will be ce ns ore d at t he la test date of t he
patie nt rec or d i n th e da ta base or t he e n d of t he st u d y  perio d , w hic he ver occ urre d first, if t he 
e n d of treat ment is n ot c o nfi r me d i n t he data base. The a nal ys is will be stratifie d b y t he li ne of 
e n d ocri ne t hera p y (e. g. first-li ne, sec o n d-line) a n d t he ti me i nter vals, i n whic h each t hera py 
starte d (t he ti me i nter vals will be defi ne d i n t he S A P).
9. 7. 1. 1. 1 0. Tre at me nt p atter n of s u bse q ue nt t he r a p y after e n d ocri ne t h er a p y, i ncl u di n g 
li ne of t her a p y a n d ty pe o f tre atme nt
T reat me nt patter n of a nti -ca nc er dr u gs f oll o wi n g t he first li ne e n d ocri ne t hera p y will be 
s u m marize d usi n g t he n u m ber a n d pr o p orti o n of patie nts ha vi n g eac h a nti-ca ncer dr u g i n
p atie nts w h o recei ve d a s u bse q ue nt t hera py after t he first li ne e n docri ne treat me nt . The 
patter n of t reat me nt re gi me n (i ncl u di n g c o m bi nati o n of a nti-ca ncer dr u gs; details will be
d escri be d i n t he S A P) will be s u m marize d i n t he sa me ma n ner. M ore o ver , t he treat me nt 
patter n of a nti-ca ncer dr u gs a n d re gi me ns f oll o wi n g t he seco n d a n d later li ne of e n d ocri ne 
t hera p y will be s u m marize d f or eac h li ne respec ti vel y if t he sa m ple size is feasi ble.
9. 7. 1. 1. 1 1. T i me t o tre at me nt f ail ure of s u bse q ue nt t her a p y after e n d ocri ne t her a p y
T i me t o treat me nt fail ure of t he s u bse que nt t hera p y  after en d ocr i ne t herap y of a n y li ne is 
defi ne d as t he ti me fr o m t he date of first prescr i pti o n of t he s u bse q ue nt t hera p y t o t he date of 
e n d of treat me nt defi ne d as t he i nitiati o n t he ne xt li ne of t hera p y. De scri pti ve s u m mary of t he 
ti me t o treat me nt fail ure will be calc ulated f or eac h li ne of t he pr e vi o us e n d ocri ne t hera p y
usi n g Ka pl a n-Meie r met h o d a n d Ka pla n -Meier c ur ves wil l be als o pr ese nte d. T i me t o 
treat me nt fail ure will be ce ns ore d at t he latest date of t he patie nt rec or d i n t he data base or t he 
e n d of t he st u d y peri o d , w hic he ver occ urre d first, if t he e n d of treat me nt is n ot c o n fir me d i n 
t he data base. 
9. 7. 1. 1. 1 2. Use of a nti bi otics a n d/ or G -C S F after i niti ati o n of tre at me nts f or A B C
T he pr o p orti o n of patie nt s prescri be d a nti bi otics a n d t he pr o p ortio n of patie nts presc ri be d G-
C S F d u ri n g treat ment f or A B C will be calc ulate d as the n u m b er of patie nts prescri be d t he 
c orres p o n di n g treat me nt di vi de d b y  t he t otal n u m ber of patie nts treate d f or A B C. T he 
a nal ys is will be e x pl ore d b y li ne of t hera p y a n d t ype o f treat me nt.
9. 8. Q u ali t y c ontr ol
T hi s st u d y is a retr os pecti ve o bser vati o nal st u d y usi n g q ualit y  c o ntr olle d data i n a pre-
e xistin g data base, a n d pri mar y data c ollecti o n will n ot be c o n d ucte d. As f or t h e d ata pr o vi de d,
q ualit y  of t he data is g uara ntee d b y M D V . All of t hese pr ocesses are c o nsiste ntl y ma na ge d 
i n-h o use.
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 8 of 2 5
Data a nal ysis will be o uts o urce d t o Cli nical St u d y S u p p ort, I nc. ( C S S). 
C S S has a pr ofes si o nal tea m t o verif y acc urac y of t he data. F or q ualit y ass ura nce of a nal y sis, 
C S S will c o n d uct c o de re vie w of all m o d ules of p r o gram f or ge n erati n g a na l ysis datasets, 
a n d perf or m a descripti ve statistics re vie w of all varia bles. P r ogr a m de vel o p me nt f or 
ge nerati n g datasets will be c o n d uc te d by t w o trai ne d a nal ys ts i n a n i n de pe n de nt ma n ner 
( d o uble pr o gra m mi n g), a n d t he co nsiste nc y  bet we e n t he datasets will be assesse d. A nal ys is 
o ut p uts, i nc lu di n g ta bles a n d fi g ures, will be ge nerated b y o ne trai ne d a nal yst a n d t heir 
q ualities re vie we d b y  an ot her trai ne d a na l yst, i n de pe n de ntl y.
9. 9. Li mit ati o ns of t he rese arc h met h o ds
T he c o m pl ete me dical hist or y  of patie nts m a y  n ot be o btai ne d beca use of t he li mite d dat a 
peri o d i n M D V data base, w hic h mea n s t hat t he patie nts ca n n ot be f oll o we d u p o nce t he y  
cha n ge h os pitals, a n d da ta of patie nts p ri or t o t he re gistrati on t o t he data base are n ot f ull y  
a vailable. T heref ore , t he past me dical hist or y  or a treat me nt histo r y m a y be missi n g f or s o me 
patie nts . Als o, it sh o ul d be n ote d t hat t he reas o n of l oss t o f oll o w - u p is n ot a vaila ble i n M D V 
data base. F or t hese reas o ns, atte n ti o n s h o ul d be paid re gar di n g i nf or mat i o n bias, w he n
i nter pretin g i nsi g hts o btai ne d a b o ut pal b ocicl i b utilizati o n i n real-w orl d setti n gs.
9. 1 0. Ot h er as pects
N ot a p plica ble
1 0. P R O T E C TI O N O F H U M A N S U B J E C T S
1 0. 1. P at ie nt i nf or m ati o n 
T hi s st u d y i n v olves data t hat e xist i n a n o n ymize d str uct u re d f or mat a n d c o ntai n n o patie nt 
pers o nal i n f or mati o n. 
1 0. 2. P atie nt c o nse nt
As t his st u d y i n v ol ves a n o n ymize d str uct ure d data, w h ich acc or di n g t o a p plic a ble le gal 
re q uire me nts d o n ot c o ntai n data s u bjec t to pri vac y  la ws, o btai ni n g i nf or me d co nse nt fr o m 
patie n ts b y Pfizer is n ot re q uire d.
1 0. 3. I nstit uti o n al re vie w b o ar d (I R B)/I n de p e n de nt et h ics co m mittee (I E C)
T here m ust be pr os pecti v e a ppr o val of t he st u d y  pr ot oc ol, pr ot oc ol a me n d me nts, a nd ot her 
rele va nt doc u me nts (e. g. inf or me d c o nse nt f or ms i f a p plica ble) fr o m t he releva nt instit uti o n al 
re vie w b oar d s (I RBs )/in de pe n de nt et hics c o m mittee s (IE C s). All c orres p o n de nce wit h t he 
I RB/I E C m u st be retai ne d.  C o pies of I R B/I E C a p pr o vals m ust be f o r war de d t o Pfizer.
1 0. 4. E t hic al c o n d uct of t he st u d y
T he st u d y will be c o n d ucte d i n acc o r da nce wit h le gal a n d re gulat or y  re quire me nts, as well as 
wit h scie ntif ic p ur pose, val ue a n d ri g or a n d f oll o w ge ne rall y acce pte d researc h pr actices 
descri be d i n G ui del i nes f or G o o d P har mac oe pi d e mi ol o g y Practices ( G P P) iss ue d b y the 
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 1 9 of 2 5
I nter nati o nal Societ y f o r P har mac oepi de m i ol o g y (IS P E) , G o o d E pi de mi ol o gical Practice 
( G E P) g ui deli nes iss ue d b y t he I nter nati o nal E pi de mi ol o gical Ass ociati o n (I E A) , G o o d 
Practices f or O utc o me s Researc h iss ue d b y t h e Inter nati o nal S ociet y f or P har mac oec o n o mics 
a n d O utc o me s Research (I S P O R) , G o o d practices f or real- worl d data st u dies of treat me nt 
a n d/o r c o m parati ve effecti ve ness: Rec o m me n dati o n s fro m t he j oi nt I S P O R -I SP E S pecial 
Tas k F orce o n re al-w o rl d e vi de nce i n health care decisi o n ma ki n g, I nter nati o nal Et hical 
G ui deli n es f or E pi de mi ol o gical Stu dies iss ue d b y  t he C o u ncil f or I nter nati o nal Or ga nizat io ns 
of Me dical Scie nces ( CI O M S) , E ur o pea n M e dici nes A ge nc y ( E M A) E uro pea n Net w or k of 
Ce ntres f o r P har mac oe pi de mi ol o g y a n d P har mac o vi gi la nce ( E N Ce P P) G ui de o n
Met h o d ol o gical St a n dar ds i n P har mac oe pi de m i ol o g y, T he E N Ce P P C o de of C o n d uct f or 
scie ntific i n de pen de nce a n d tra ns pare nc y i n t he c o n d uct of p ha r mac oe pi de mi ol o gical a n d 
p har mac o vi gila nce st u dies , F o o d a n d Dr u g A d mi nis trati o n ( F D A) G ui da nce f or I n d ustr y: 
G o o d P har mac o vi gila n ce Practices a n d P ha r mac oe pi de mi olo gic Assess me nt , F D A G ui da nce 
f or I n d ustr y a n d F D A St aff: Best Practices f or C o n d ucti n g a n d Re p orti n g 
P har mac oe pi de mi ol o gic Safet y  St u dies Usin g Electr o nic Healt hcar e Data, F D A G ui d a nce f or 
I n d ustr y: Patie nt-Re p orte d O utc o me Meas ur es: Use i n Me dic al Pr o d uct De vel o p ment t o 
S u p p ort L a beli n g Clai ms .
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E
R E A C TI O N S
T his st u d y  does n ot i n v ol ve data c ollec ti o n o n i n di vi d ual pati e nts b y t heir treati n g healt hcare 
pr ofe ssi o nals a n d t he M D V data u se d i n t his st u dy d oes n o t i nte n d t o i de ntif y pr o d uct safet y 
i nf or mati on .  T he M D V data
f or t his st u d y will be c o mp leted o nli ne via a sec ure we bsite   
T he M D V data
d oe s n ot pr o vi de a free te xt fiel d w here st u d y partici pa nts c o ul d s pecif y 
i nf or matio n t hat m a y c o nstit ute pr o d uct saf et y i nf or ma ti o n.  F urt her, r o uti ne c o m m u nicatio n 
wit h st u d y partici pa nts via e mail or p h o ne wi t h C S S is n ot e x pected d uri n g t he c o n d uct of t he
st u dy.  H o we ver, it is p o ssi ble t hat a st u d y partici pa nt ma y  v ol u nteer pr o d uct safety 
i nf or mati o n t o C S S w hile i n c o n versati o n a b o ut t he M D V data
f or a n y ot her reas o n (e. g., 
see ki n g i nf or mati o n a b o ut t he pur p ose of t he st u d y) ; this i nf or mati o n m ust be re p orte d as 
descri be d bel o w.
T he f oll o wi n g safet y e ve nts m ust be re p orte d o n t he no n -i nter ve nti o nal stu d y  (NI S) a d ve rse 
e ve nt m o nit ori n g ( A E M) Re p ort F or m: seri o u s a n d no n -seri o us a d verse e ve nts ( A E s) w he n
ass ociate d wit h t he use of t he Pfizer pr o d uct, a n d s ce nari os i n v ol vi n g e x p os ure d uri n g 
pre g na nc y , e x p os ure d uri n g breast fee di n g, me dicati o n err or, o ver d ose, mis use, 
e xtra vasatio n, lac k of efficac y a n d occ u pati o n al e x p os ure ( all re p ort a ble, re g ar dless of 
w he t her ass oci ate d wit h a n A E) , w he n ass ociate d wit h t he use of a Pfizer pr o d uct.
I n t he e vent t hat a st u d y  participa nt v ol u nteer s pro d uct saf et y i nf or ma ti o n, C S S m ust
c o m plete t he NI S A E M Re p ort F or m a n d s u b mit t o Pfize r wit hi n 2 4 h o urs of bec o mi n g 
a ware o f t he safet y e ve nt.  I ncl u de d i n t he c o m pleti o n of t he NI S A E M Re p ort F or m is t he 
st u d y partici pa nt’s c o ntact i nf or mati o n; c o m plete c o ntact inf or mati o n s h o uld be o bta i ne d s o 
t hat, o nce t he NI S A E M Re p ort F or m is se nt t o Pfizer, t he NI S A E M Re p ort F or m ca n be
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 2 0 of 2 5
assesse d a n d pr ocesse d acc or di n g t o Pfizer’s sta ndar d o perati n g pr oce d ur es, i ncl u di n g 
req uests f or f oll o w -u p t o t he st u d y participa nt. 
C S S w h o will ser ve t o c o de re vie w of all m o d ules of pr o gra m for ge nerati n g a nal y sis 
datasets a n d perf or m a descri pti v e statistics re vie w of al l varia bles m ust c o m plete t he 
f oll o wi n g Pfizer trai nin g re q uire me nts:   

“ Y R R Tr ai ni n g f o r Ve n d ors Worki n g o n Pfizer St u dies (e xcl u di n g i nterve nti o n al 
cli nic al st u dies a n d n o n-i nterve nti on al pri m ary d at a c ollecti o n st u dies wit h 
sites/investi g at ors) ”. 
T he se trai ni n gs m ust be c o m ple te d by C S S pri or t o t he start of data collecti o n.  All trai ni n gs 
i ncl u de a “ C o nfir mati o n of Trai ni n g Cert ificate” (f or si g nature b y t he trai nee) as a rec or d of 
co m plet i o n of t he trai ni n g, w hic h m ust be ke pt in a retrie va ble f or ma t.  T he st u d y ve n d or will 
als o pr o vi de c o pies of all si g ne d trai nin g certificates t o Pfiz er.  
Re -trai ni n g m ust be c o m plete d o n a n an n ual bas is usi n g t he m ost c urre nt Y o ur Re p orti n g 
Res p o n si bilities trai ni n g materials.
1 2. P L A N S F O R D IS S E M I N A TI N G A N D C O M M U NI C ATI N G S T U D Y R E S U L T S
I n t he eve nt of a n y  pr o hi bitio n or restricti o n i m p ose d (e. g. cli nical h ol d) b y a n a p plic a ble 
co m p ete nt aut h o rity i n a n y area of t he worl d, or if M D V
is a ware of a ny ne w i nf or mati o n 
w hic h mi g ht i nfl ue nce t he e val u ati on of t he be nefits a n d ris ks of a Pfizer pr o d uct, Pfiz er 
s h o ul d be i nf orme d i m me diately.   
1 3. R E F E R E N C E S
1
T he lat est ca ncer ga nj o h o .j p (Nati o nal Ca ncer Ce nt er, the C e nter f or Ca ncer C o ntr ol 
a n d I nf or mati o n Ser vi ces ); htt p:// ga nj o h o.j p/re g _stat/statistics/stat/s u m mar y. ht ml.
2
T he Ja pa nese Breast Ca ncer S ociety. Cli nical Practice G u i deli nes f or Breast Ca ncer 
2 0 1 8; htt p://j bcs. gr.j p/ g ui dli ne/ 2 0 1 8/
3
Nati o n al cancer i nst it ute. S ur v eilla nce, E pi de mi ol o g y, a n d E n d Resu lts Pro gra m. 
S E E R Stat Fact S heets: Fe male Br east Ca ncer.; 
htt p://se er.ca ncer. g o v/statfacts/ ht m l/ breast. ht ml .
4
Metast atic Breast Ca ncer Net w or k. E d ucati n g Em p o weri n g A d v ocati n g, E d uca ti o n, 
I nci de nce a n d I nci d e nce Rates; htt p:// m bc n. or g/e d ucati o n/cate g or y /i nci dence -a n d -
i nci de nce-rates.
5
Har ve y  J M, et al. Estr o ge n rece pt or stat us b y i m m u n o hist oc he mistr y is s u peri or t o t he
liga n d -bi n di n g assa y f or pre dicti n g res p o nse t o a dj u va nt e n d ocri ne t hera p y in bre ast 
ca ncer. J Cli n Onc ol . 1 9 9 9; 1 7: 1 4 7 4 - 8 1.
6
Fi n n R S, e t al. P al b ocicli b a n d Letr oz ole i n A d va nce d Br east Ca ncer. N E n gl J Me d. 
2 0 1 6; 3 7 5: 1 9 2 5 - 3 6.
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b ocicli b
A 5 4 8 1 1 1 5 N O N -I N T E R VE N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy
1 5 -A u g -2 0 1 8
Pa ge 2 1 of 2 5
7
T ur ner N C, et al. Pal b ocic li b i n H or m o ne- Rece pt or-P ositi ve A d va nc e d Breast Ca ncer.
N E n gl J Me d. 2 0 1 5; 3 7 3: 2 0 9 - 1 9.
8 
Crist ofa nilli M, et al. F ul vestra nt pl us pal b oc icli b vers us f ul vestra nt pl us place b o f or 
treat me nt of h or m o ne -rece ptor- p ositi ve, H E R 2 -ne gati ve metas tatic breast ca ncer that 
pr o gresse d o n pre vi o us e n d ocri ne t hera p y ( P A L O M A- 3): fi nal a nal ysis of t he 
m ultice nt re, d o u ble-bli n d, p hase 3 ra n d o mise d c o ntr olle d trial. La ncet O nc ol. 
2 0 1 6; 1 7: 4 2 5 - 3 9.
9
L o i bl S, et al. Pal b ocicli b C o m bi ne d wit h F ul vestra nt i n Pre me n o pa usal W o me n w it h
A d va nce d Bre ast Ca ncer a n d Pri or Pr o gressi o n o n E n d oc ri ne T hera p y:  P A L O M A- 3 
Re s ults. O n c ol o gist. 2 0 1 7; 2 2: 1 0 2 8 - 3 8.
1 0
Ta m ura K, M u kai
H, Na it o Y, et al. P hase I st u d y of pal b o ciclib, a c y cli n-de pe n de nt
ki nase 4/ 6 i n hi bit or, i n J a pa nese patie nts. Ca nce r Sci 1 0 7 ( 2 0 1 6) 7 5 5 – 6 3 .
1 4. LI S T O F T A B L E S
Ta ble 1 Data p e rio d
Ta ble 2 Varia ble s
1 5. L I S T O F FI G U R E S
N ot a p plica ble
A N N E X 1 . A D DI TI O N A L I N F O R M A TI O N
A p pe n di x 1: Al g o rit h m t o defi ne t he first li ne treat me nt f or a d va n ce d breast ca ncer
A p pe n di x 2: Li st of Treat me nt Dru gs f or Bre ast Ca ncer
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b oci cli b
A 5 4 8 1 1 1 5 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy 1 5 -A u g -2 0 1 8
Pa ge 2 2 of 2 5
A p p e nd i x 1: Alg o rit h m t o defi ne t he first li ne treat me nt f or a d va nce d breast ca ncer
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b oci cli b
A 5 4 8 1 1 1 5 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy 1 5 -A u g -2 0 1 8
Pa ge 2 3 of 2 5
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b oci cli b
A 5 4 8 1 1 1 5 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy 1 5 -A u g -2 0 1 8
Pa ge 2 4 of 2 5
A p p e ndi x 2: Li st of Treat m e nt Dr u gs f or Breast Ca ncer
( 1) E n d ocri ne t her a p y dr u g s
G e neric n a me
A b bre vi ati o n
Tr a de n a me
R o ute of a d mi nistr ati o n
T he r a pe utic c a te g ory
A nastr oz ole
A N A
A ri mi de x, ot hers *
Oral
Ar o matase i n h ibit or
E xe mesta ne
E X E
Ar o masi n, ot hers *
Or al
Ar o matase i n hi bit or
G o sereli n acetate a)
Z O L
Z ola de x
S u bc uta ne o us i nject i o n
L H -R H a g o nis t
Ta m o xife n citrate
T A M
N ol va de x, ot hers *
Oral
Se lecti ve estr o ge n rece pt or m o d ulat or
T ore mife ne citrate
T O R
Farest o n, o thers *
Oral
Selecti ve estr o ge n rece pt or m o d u lat or
F ul vestra nt
F U L
Fa sl o de x
I ntra m usc ular i njecti o n
Sele cti ve estr o ge n rece pt or d o w nre gulat or
Me dr o x y pr o gester o ne acetate 
M P A
H ysr o n - h 20 0, ot hers *
Oral
Oral a nt i ne o plastic pr o gesti n 
Le u pr oreli n acetate a)
L P R
L u pr o n, ot hers *
S u bc uta ne o us i njecti o n
L H - RH a g o nist
Letr oz ole
L E T
Fe mara
Oral
Ar o matase i n hi bit or
L H - R H: L utei n izin g H or m o ne -Re leasi n g H or m o ne         a) G osereli n ace tate a n d Le u pr oreli n acetate are excl u de d fr o m t he treat me nt dr u gs f or breast ca n cer f or t his st u d y.
( 2) A nti b o d y t her a pe utic d r ugs
Ge neric n a me
A b bre vi ati o n
Tr a de n a me
R o ute of a d mi nistr ati o n
T her a pe ut ic c ate g or y
De n os u ma b a)
D m a b
R A N M A R K
S u bc uta ne o us i nject i o n
H u ma n a nti-R A N K L m o n o cl o nal a nti b o d y
Tra st uz u ma b
Herce pti n
I ntra ve n o us i njecti o n
H u ma nize d a nti -H E R 2 m o n ocl o nal a nti b o d y
Trast uz u ma b e mta nsi ne
T- D M 1
Ka dc yla
I ntra ve n o us i njecti on
Trast uz u ma b a n d D M 1 a nti b o d y – dr u g c o nj u gate 
Be vaciz u ma b
B ma b
A vasti n
I ntra ve no us i njecti o n 
H u ma nize d a nti-V E G F m o n ocl o nal a nti b o d y
Pert uz u ma b
Perj eta
I ntra ve n o us i njecti o n 
H u ma nize d a nti - HE R 2 m o n ocl o nal a nti b o d y
Trast uz u ma b Der u xteca n
T- D X d
E n hert u
I ntra ven o us i njecti o n 
Trast u z u ma b an d D X d a nti b o d y– d r u g c o nj u gate
a) De n os u ma b is e xcl u d ed fr o m t he t reat me nt dr u gs f or breast ca ncer f or t his st u d y.
( 3) S m all m olec ul ar c o m p o u n ds
Ge ner ic n a me
A b bre vi ati o n
Tr a de n a m e
R o u te of a d mi nistr ati o n
T her a pe utic c ate g or y
E ver oli m us
Afi nit or
Or al
m T O R i n hi bit or
Pal b o cicli b
I bra nce
O ral
C D K 4/ 6 i n hi bit or
La p ati ni b t osilate h y drate
T y ker b
Oral
H E R 1 / H E R 2 t yr osi ne ki nase i n hi bit or
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)

Pal b oci cli b
A 5 4 8 1 1 1 5 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Pr ot oc ol versi o n 4 . 0, 3 1 Marc h
2 0 2 1
P F I Z E R CO N FI D E N TI A L
C T 2 4 -WI -G L 0 2 - R F 0 2 1. 0 N o n -I nterve ntio n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C olle cti o n St u dy 1 5 -A u g -2 0 1 8
Pa ge 2 5 of 2 5
A b e macicl i b
Ve rze ni o  
Oral
C D K 4/ 6 i n hi bit or
O lapa ri b
L y n parza
O ral
P A R P 1 i n hi bit or
( 4) C yt ot o xic c h e m ot her a p y dr u gs
G e neric n a me
A b bre vi ati o n
Tr a de n a me
R o ute of a d mi nistr ati o n
T h er a pe utic c ate g or y
Iri n oteca n h y dr oc hl ori de h y drate
C P T - 1 1
Ca m pt o, ot h ers *
I ntra ve n o us i njecti o n
T o p ois o merase I i n hi bit or
E pi r u bicin h y dr oc hl ori de
E PI
P har m or u bici n, ot hers * 
I ntra ve n o us i njec ti o n  
A ntit um or a nti bi ot ic
Eri b uli n mes y late
H A L
Hala ve n
I ntra ve no us i njec ti o n
Micr ot u b ule i n hi bit or
Ca pe cita bi ne
C A P
Xel o da
Ora l
A nti meta b o lite
Car b o plati n
C B D C A
Para plati n, ot hers *
I ntra ve n o us i njecti o n
Plati n u m c o m p o u n d
Ge mcita bi ne h y dr oc hl ori de
G E M
Ge mzar, ot h ers *
I ntra ven o us 
A nti meta b ol ite
C ycl o p h os p ha mi d e h y d rate
C P A
E n d o xa n
Oral/I ntra ve n o us i njecti o n
Al k yl ati n g a ge nt
Ci s plati n
C D D P
Bri pla ti n, ot hers *
I ntra ve n o us i njecti o n
A n tine o plast ic
Te gaf ur – uracil
U F T
U F T
Oral
A nti meta b o lite
Te gaf ur – gi me racil– oterac il p otassi u m
S- 1
T S -1, ot her s *
Oral
A nti meta b oli te
D o xifl uri d i ne
5 ′ D F U R
F urt ul o n
Oral
A nti meta b olite
D o x or u bici n h y dr o c hl ori de
A D M
A dr iaci n, ot hers *
I ntra ve n o us i njecti o n
A nti t u m or a nti bi otic
D oceta xel h y drate
D T X
Ta x otere , ot hers *
I ntra ve n o us i njecti o n
Ta x oi d
Paclita xel
P T X
Ta x ol, ot hers *
I ntra ve n ou s i njecti o n
T a x oi d
N a b- Paclita xel ( Al b mi n s us pe n de d)
na b -P T X
A bra x a ne
I ntra ve no us i nj ecti o n
Ta x oi d
Vi n orel bi ne tartrate
V N B
N a vel bi ne, ot hers *
I ntra ve n o us i njecti o n
Vi nca al kal oi d
fl u or o uracil
5- F U
5- F U
I ntra ve n o us i njecti o n 
a nti meta b olite
Mit o m yci n
C
M M C
Mit o m yci n S
I ntra ve n o us i njecti o n
a ntit u m or a nti bi otic
mit o xa n tr one h y dr oc hl ori de
MI T
N o va ntr o ne
I ntra ve n o us i njecti on
a ntit u m or a nti bi otic
met h otre xate
M T X
met h otre xate
I ntra ve n o us i njecti o n
a ntif olic
0 9 0 1 7 7 e 1 9 6 a 0 d 5f e\ A p pr o v e d\ A p pr o v e d O n: 2 6- M ar- 2 0 2 1 0 1: 3 7 ( G M T)