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2012/07/07!CSP"HOR67 89=>?@AB
CDEFGHIJKLMNOPQRSTU =>PQV7WXTYZZ[\]^_C`Eab cdefHghf+i)jklA)mn&oL
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Cli i l Q ti
Clinical!Question:!=>¸ã:=>¸ã:ÄÅÆ)Ç0È#É45ÊÄ4 %ÄÅÆ)Ç0È#É45ÊÄ4Ë%£ÌÍÎO¾ÏÐÑÒÓÔÕUÖV×ØÙ*j)#¡äåæcÑÒçèÖV×ØHÆ)LUÑÙ*j)#ÚÃ45éê'Ûë3=>/ìíî+â

ÚÃ'ÛÑ.Ü/Õ'£ÚÃ'ÛÑ.Ü/Õ'cÑÒÕºÝÞßà«¬­3á¼­Õ'Ñ£

Evidence!Based!MedicineHEBMLeØï¼oð'Û£Æ)ÚÃ4«¼Õ'+âÌ
½O¾££££ÌEBMñòó*ôõö 5A*ôõö0O ÍÎ÷øAssess!your!patient*ôõöùO ú:ûüÖHýþÿ L

Ask!clinical/research!question*ô ö! ú:"¼5#$%&*ôõö!OA i d b t id
Acquired!best!evidence*ôõö'O ()*­#$+,/-.

Appraise the evidence
Appraise!the!evidence*ôõöO #$ÍÎ/ßà

Apply!evidence!to!patient!careú:ûüÖOPECO (PICO)
ú:ûüÖOPECO!(PICO)

P:!Patient!!12«+£*ôõöóO *ôõöù0÷ø

E:!Exposure/Intervention!34«+£
C:!Comparison! 56«+£
O:!Outcome rs«+£ÑÒ=>WXÕ÷øY*ÛZ[\<·]3
! 19966UASCO^À¿À)_`!

*ôõöùUú:ûüÖOPECO!(PICO)
Patient:!54EUFG£PS0£
cdfK'6  ¡!7U°±«4
cdfK'6U
¡!7 °±«4ER",!PgR",!HER28G£a)+Exposure:!Æ)Ç0ÈÙ*j)#ÚÃ"ÍÎ\<·]! &hEU&hGH! KLMNQOLHPatient!Reported!Outcome:!PRO)KLMNQOLHPatient Reported Outcome: PRO)

CComparison:!Æ)Ç0ÈÊéêiÆ)Ç0ÈÊéê=>/ìí

Outcome: Ù*j)ÚÃA*Á39k:;õ<Outcome:!Ù*j)ÚÃA*Á39k:;õ<=×#>?'Û¸Õ@A«#$ofã:

2BCU=DEâUF&hGHUIJÃUKLMNQOL! IJÃUbG Hcd/e.UPRO)"JOG"

PQ\<·]! PQPQEUTUV&hGH
PQPQE TUV&hGH «$Hcd/e.L! ÙÀB»·UPQ»·«$Hcd/e.L

JOG PQPQÖRsSTUVGHâJOGUPQPQÖRsSTUVGHâg hçe.÷øißjUkl()mÀ)<Ñ@A¡cÑÒ=Û+âopqx^rsty^r^yuqvpq^svqw^wxyq^xvvp^rsvp^wxxvpuqvp^wwxqwuy^r^xququqvw^xuq^wupw
}px^  q^u\^yz|^`[[{! 1973"1982,!MD!Anderson,!1,581Pts.!MBC,, ,! 1st line!)*¿ÀÁA)|}~)¡äåæcÑÒn±" CR!rate,!16.6%" 56HCR#4­°2UF3.1%" 206HCR#4­°2UF1.6%

12! "#$%&'()*+,-../012 345"#$%&
Goal of therapy

678+"#$%&9:;<=>,-?@ABCDEHR

1991 92

438F

1

1994 95

450F

0 97
0.97

0 65
0.65

1997 98

564F

0.84

0.011

1999 01

667F

0.72

<0.001PUVW*XY*Z[AIs,!GHIJ+K;LMNJOPQRST?@AB'\]^V' J<^V'9J<_;``
Quality of Life'abc12
Quality!of!Life'abc12
Disease of the Breast, 4th edition,

Chia!SK!et!al.!!Cancer,!110,!2007

de'fgQhXSij
Patient:!54k+lmnPS0n$op)q,r s"#tu ^Vv$op)q,r+s"#tu+^Vv
ER ,!PgR ,!HER2wmn

1314}Mth de0 43' Acquired!best!evidence
ECOG 2100hNEJM, 2007

AVADOh JCO, 2010Exposure:!GHIJxyz0{|}NJ~OP

Comparison: GHIJxyz'Comparison:!GHIJxyz'
RIBBON!1h JCO, 2011

Outcome: ?@AB'\]ijE2100: )*+,-./

ECOG 2100: , !, QPFS0123"#$%㦹㽊䣑ቑ慱䲊␜䤉ℂሯቶn=722
⻳⒴⥯⷟:• 䎰䡔䞮ⷧ㦮栢• 慱䲊⊚㟿
• 嫢㈛ቑ▥ⷵ䣑㽤(ሥቭ vs ቍሺ)• ኸወ኿ዐ♦⹈⇢ቑ䤉䚍ኜኊኚዙወ

⬦㌹ቡቊ倨倩,⬦㌹ቡቊ倨倩
⬦㌹㈛ቑቿክኖኞዐ
∎䞷ቒ崜ቤቍሧ

ኜኊኚዙወ +ቿክኖኞዐ
10 mg/kg 2拀㹝⬦㌹ቡቊ倨倩

! 4656-123"#$%-78+,! !"#$%DEFG5HA• r:!PFS?@ABr: PFS?@AB'¡'r:!ORR¢i£,!OS !"#$%&,
quality
lit off life,lif safety
f t '!(&Miller et al. NEJM 2007

17

Objective Response Rate 9:-;<+,=>?@ABC&IJKLMNOP
021.2%
18
QRSTUVWP 036.9%
p< 0.001
Miller KD et al. NEJM 2007

AVADOXY: )*+, (PFS) -./AVADOXY: Z[\]^U_`LM2abcXY

rstu
rstu:
• ef|}• IJ~U-)*/*5?$%• • MU-i

IJKd M
IJKdLM
100mg/m2+ Z[\] 3lm
IJKdLM+QRSTU7.5mg/kg
3lm23 p)*w

no)*pF!vD
QRSTUwxyz{

IJKdLM+QRSTU15mg/kg
3lm

15mg/kgVWPp4n56123"#$%=78A: PFS (123"#$%&o: +, +$%, !"#$%, quality of life

Pivot et al. JCO 2010

AVADOXY: ¡-¢!"#$% &'(Z[\]P= 8.2 6
QRSTUVW(7.5mg/kg)
Q
TUVW(g/ g) = 9.0

6

QRSTUVW(15mg/kg) = 10.1

6

RIBBON 1CDEFG@H5678I@JKLM2NOPCD]"#!
^_`abcVde fghij
ersfghijtuvwm• xy*+,• QR#S• ^_

QR#S0T#UVWX:YZ[\@no[pq@no<@>6qG@l gmfef hij=kefghij=kqo)* (n=705)x

–OS0!"#$%QR#S k<=>?@hz{
QR#S k<=>?@hz{|}~2 !"#$%&'()*+,• QR#S!)*+,-./01234
56789= 31.9:;<=>?@AB(7 5mg/kg) = 30<=>?@AB(7.5mg/kg)
30.8
8 :;
<=>?@AB(15mg/kg) = 30.2 :; PFS (x|}*+,-:: $, )*+,-*+)Pivot et al. JCO 2010

Robert NJ et al. JCO 2011

RIBBON 1CD:!"#$% (PFS)!!'(QR#S¡¢£[pq@/<@>6qG@¤B9PFS:!x|}*+,-OS:!)*+,-¥x|}*+,-V¦2;§¨¢4¥)*+,- *+./01234¥)*+,-©*+./01234
Robert NJ et al. JCO 2011

Valachis A et al.

]^&_`abcde<=>?@AB.!"#$%&'()*+,&-.$%/012345678&9':;<=/>?@)*+,A>?@)*+,BCD&EF5G4H/IJKL&+,M

Patient: 54f5ghUPS0U
ijkl6m= nopqr st04
ijkl6m=5nopqr5st04
ER", PgR", HER2uhU
Exposure: vwxyz{|}~ye>?@)*+,&NO0-.$%PQRST1!U
Comparison: vwxyz{|& 
E2100: (6VW5AVADO:(2VW5RIBBON"1:(1VWXY Z $%P[H0!
XY&Z\$%P[H0!

Outcome: cde

E2100: 21
21.2%
2% vs 36.9%,
36 9% AVADO: 46
46.4%
4% vs 64.1%
64 1%

E210078: cde&

AVADO78: cde&

Bevacizumab
L?!hs[

[5P]^&_`abÁÂÃÄQOLcde&'(vwxy¢£&cde" ¤¥¦5§¨5©«¬0­¡?Patient: 54f5ghUPS0U
ijkl6m= nopqr st04
ijkl6m=5nopqr5st04
ER", PgR", HER2uhU" vw®´¯L/h°±²³bG3"4,vw® ¯L/h°±²³ G3 4 (20%" vw®µ´¯L/¶XbG3"4, (3%Exposure: vwxyz{|}~ye~ye42·¸" [bG3"4,[bG3 4 (5"15%(5 15%Comparison: vwxyz{|& " bG3"4, (3%" bG3"4, (2%Outcome: ÁÂÃÄQOL¹G (Grade) 3, 4&cdeb"#&º»¼½¾P¿'0cdeÀ]^&_`abÁÂÃÄQOL

E2100: HRQOLQ

Patient: 54f5ghUPS0U
ijkl6m= nopqr st04
ijkl6m=5nopqr5st04
ER", PgR", HER2uhU
Exposure: vwxyz{|}~ye

FACT!General
Å04

Trial Outcome Index (TOI)Å04

Comparison: vwxyz{|& Outcome: ÁÂÃÄQOLÆÇÈÉÊÈËÌÈÍÎ

ÆÇÈÉÊÈiPÏÐÑÒÓ 32

ÛÜ!"#$%&

E2100: HRQOLªÕÖ5×ØÙ'()*+,-./01/2345

67/89:;<=>?@ABCDEFG?B 6H$IJK
67/89:;<=>?@ABCDEFG?BL6H$IJK
2%MNLOPQR:;K25 30STE?U(VWXY<Z[3\]^E_L:;/`a9KRb8cE?Ude )*+,
de()*+,
67/89deBfgGEhi?jIJK20 50%E?BLklKmnQRopELOP6 8STEqrKstuv3G?U
Z[3\]^LdeBfgGEhi?jIJB40 65%/wG9Pacli.+Bevacizum
Pacli.
Bevacizum

17Ú
19%

33Ú
37.1%

Pacli.

30.7%

45.1%

''!"#$%&-}F5()*+,-~L[L/Q

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qrBuv?jGE$CxB1 6ST=tG?U
qrBuv3\]^K y$zB"{<|?@A/R9G?
qrBuv3\]^KLy$zB"{<|?@A/R9G?U

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2%/0¡G?UÄVÅÆÇÈ45kg
1.5m2
135mg
450mg

[Ã100mg
30mg
100mg
30mg

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¥30,505¥10,264¥15,474¥5,587

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¥30,505¥20,528¥15,474¥11,174

100mg
400mg

¥45,563¥173,511

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¥37,483!

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,¥59,430!
,¥24,600!
,¥35,400¥37,483!
¥37,483!
¥24,600!
¥35,400¥83,400¥44,400!
¥24,600!

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¥59,430¥37,483¥83,792¥59,430¥37,483¥83,792¥59,430¥37,483¥83,792¥59,430¥37,483¥44,400¥59,430¥37,483¥44,400¥59,430¥37,483¥44,400

Discussion point
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