??NSCLC????????

1
??NSCLC????????

• ???
• ???????

2

• ????
• NSCLC?????
• NSCLC?????
• NSCLC?????

3
???????

• ????????????1,200,000?
• ?2025?,??NSCLC??80
• ??????,???????????????
• ?30?????????????,???????????????????38,???16????
  ?
• 80?????NSCLC
• ???????15

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??NSCLC????
9
??NSCLC??????FDA????
?? ?? ?? ???
????2002
????2003
????????2004
????1999
???????1998
?????2006
????1994
12
nab-p 2010
??1989
??1978
8 - 10
??OS (?)
6
2 - 4
1970
1980
1990
2000
??????
????
??
???????
????NSCLC????
10
??NSCLC??????
????/??????NSCLC
EGFR????
EGFR???? ???
???
??
???? ??????
???? ?????
????? ?????
???? ?????
???? ??????
???? ?????
??
??????
????
????
?????
????
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????
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??
Gandara clinical Lung CA 2009
11
nab-P/C?P/C????????

• ?????????
• 100mg/m2 ,?1?8?15?
• ??AUC 6,?1?
• ????
• N525

???? PS 0-1 ?b/ ?? NSCLC N1,050
11

• ??????
• 200mg/m2 ,?1?
• ??AUC 6,?1?
• ???????????
• N525

• ????
• ??(?b? ??)
• ??(lt70?gt70)
• ??
• ???(????\?????)
• ??

?????
12
????

• ????
• ?????????RECIST????????
• ????????(CR,PR)
• ????
• ?????????
• ?????CRPR????(SD)16?
• ???(NCI CTCAE V3)

13
??????

• ??????
• ???/???????b/ ??NSCLC????
• ECOG??????0?1
• ??RECIST????,????????
• ????????????
• ???????????????(????????1??????)
• ??????
• ????????(???????????????)
• ?????????2?

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??????
??? 45(29???)
??? 4(6???)
??? 24(16???)
?? 12(25???)
?? 14(21???)
????2007?12?14?-2009?8?1? ????
2007?12?14?-2009?7?14? ????18?? ????1052? ?????
1052? ????1038?
???? 1(5???)
15
????(1)
Nab-P/C (n521) P/C (n531) ???? (n1052)
??,??(??)?? 60(28,81) 60(24,84) 60(24,84)
lt70?,n() 448(86) 449(85) 897(85)
70?,n() 73(14) 82(15) 155(15)
??,n() 129(25) 134(25) 263(25)
ECOG,n()
0 133(26) 113(21) 246(23)
1 385(74) 416(78) 801(76)
???????,n()
?? 254(49) 264(50) 518(49)
????? 228(44) 221(42) 449(43)
???? 9(2) 13(2) 22(2)
?? 29(6) 33(6) 62(6)
??????,n()
?? 99(19) 107(20) 206(20)
?? 421(81) 424(80) 845(80)
??1???????
16
????(2)
Nab-P/C (n521) P/C (n531) ???? (n1052)
???????,n() 12(2) 8(2) 20(2)
????,n() 513 521 1034
???? 138(27) 144(28) 282(27)
??? 165(32) 146(28) 311(30)
???? 210(41) 231(44) 441(43)
17
????ORR
RR 1.31 (1.082-1.593) P 0.005
RR 1.26 (1.060-1.496) P 0.008
Nab-P/C(n521)
37
P/C(n531)
33
30
????
25
???????
?????
18
????ORR--?????
??
???
P 0.060
P0.808
P 0.069
Plt0.001
Nab-P/C
P/C
41
37
37
????
26
30
29
25
24
???????
?????
???????
?????
n228
n221
n292
n310
19
??

• ???????????,?????????????????????????
  (33vs.25,Plt0.001)
• ??????????????????????????????????41?24
  (Plt0.001)
• ??????????????????????,?????????????????????
• ?????????,???????????????????????
• 2010????????????

20
??NSCLC?????
21
????????
Treatment
OS
1YS
????
TTP??
DCR
???????? ????,???,?????
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?????????????III?????
???? ?????? ????? ????? ?????
???? TAX. 317 TAX. 320 JMEI
???? JMEI
???? ISEL INTEREST V15-32 ISTANA
???? BR.21 Hellenic
24
TAX 317????
????75mg/m2????NSCLC???????
J Clin Oncol 2000
25
TAX 317??????
J Clin Oncol 2000
26
??????NSCLC?????? (JMEI)
J Clin Oncol 2004
27
??????NSCLC???????? (JMEI)
J Clin Oncol 2004
28
??NSCLC???????
FIGURES FACTS
29
???? BR21 (??????)
????6.7M ,???4.7M
Shepherd et al, 2005
30
???? BR21
Shepherd et al, 2005
31
Pemetrexed Vs. Erlotinib
L. Vamvakas et al, 2010
32
Pemetrexed Vs. Erlotinib
L. Vamvakas et al, 2010
33
ISEL????

• ??
• ???/???????????
• ?????1-2???????????????????
• ???????????????????lt90????????

• ????
• ????
• ?????
• ????
• ???????
• ?????
• ????
• ?????

???? 250 mg/? ??????
? ? ? ? 21
??? ??????

• ISEL ?????????III?????????(28???,210???)
• ISEL ???1692,?????342,ISEL????????
• MST 5.6 vs. 5.1 ?, p 0.11?????MST 6.3 vs.
  5.4 ?, p 0.07

Thatcher et al 2005
34
ISEL??????????300??????
???(n235) ???(n107)
?? () 59.6 59.8
??? () 41.3 41.1
ECOG PS ()
0-1 / 2 / 3 72.3 / 21.7 / 6.0 72.0 / 20.6 / 7.5
?? / ?? () 64.3 / 23.4 63.5 / 23.4
?????????? ()
CR/PR / SD / PD 21.3 / 34.5 / 34.9 20.6 / 31.8 / 39.3
Chang A, et al. J Thorac Oncol 2006 1847-855.
???BAC
35
??????????????
??????????????????? ????????NSCLC?????
Chang A, et al. J Thorac Oncol 2006 1847-855.
36
??EGFR-TKI ?????????
37
????????????????NSCLC???????????????

• Comparison of Gefitinib and Docetaxel in patients
  with pretreated advanced NSCLC
• Meta-Analysis from four clinical trials

Shepherd FA, et al. 2009 ASCO Abstract 8011.
TAX317?BR21 ??????
38
???????????????????????
????
????
P0.5773
39
????????????????? (????)
?????????????????HR lt1?????????????
Shepherd FA, et al. 2009 wclc.
40
?????????????????? (????)
Shepherd FA, et al. 2009 wclc.
41
?????????/???
?????????
?? ???/??? 95 CI P?
OS(n384) 1.084 0.821-1.430 0.5709
PFS(n334) 0.594 0.462-0.765 lt0.0001
ORR(n334) 4.591 2.512-8.388 lt0.0001
?? ???/??? 95 CI P?
OS(n579) 1.043 0.854-1.275 0.6780
PFS(n505) 0.991 0.813-1.208 0.9295
ORR(n505) 1.574 0.904-2.743 0.1092
????
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????????????????
?????????
??? ???/??? 95 CI P?
OS(n382) 0.941 0.710-1.248 0.6733
PFS(n337) 0.623 0.485-0.802 0.0002
ORR(n337) 3.627 2.054-6.405 lt0.0001
?? ???/??? 95 CI P?
OS(n581) 1.068 0.876-1.303 0.5166
PFS(n502) 0.966 0.792-1.178 0.7302
ORR(n502) 1.868 1.050-3.324 0.0334
????
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??????????????
?????????
?? ???/??? 95 CI P?
OS(n712) 1.104 0.908-1.343 0.3211
PFS(n617) 0.784 0.653-0.941 0.0088
ORR(n617) 2.396 1.557-3.688 lt0.0001
??? ???/??? 95 CI P?
OS(n251) 0.955 0.716-1.273 0.7532
PFS(n222) 0.907 0.670-1.228 0.5286
ORR(n222) 4.540 1.401-14.712 0.0117
????
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??????
????FACT-L?????
Cufer T, et al. Anti-Cancer Drugs 2006
17401-409. Maruyama R, et al. J Clin Oncol 2008
264244-4252. Kim ES, et al. Lancet 2008
3721809-1818. Lee DH, et al. presented at
ASCO2008.
45
????????
3/4????????????????
Cufer T, et al. Anti-Cancer Drugs 2006
17401-409. Maruyama R, et al. J Clin Oncol 2008
264244-4252. Kim ES, et al. Lancet 2008
3721809-1818.
ISTANA??????
46
??????????????

• ????????
• ??????HR0.81,??????????19?????,P0.0059
• ??????????????????????2.64?, Plt0.0001
• ????????,??????

47
TKI?????????????
???? ???? ??? ????
?????????III ????? ?? II? INTEREST Hellenic
?????????III ????? ?? II? V-15-32 Hellenic
?????????III ????? ?? II? ISTANA Hellenic
?????????III ????? ?? II? IPASS ??
?????????III ????? ?? II? NEJGSG002 ??
?????????III ????? ?? II? WJTOG3405 ??
?????????III ????? ?? II? EORTC08021 ??
????????????? ?? I? 2009ASCO ??
????????????? ?? I? 2009WCLC ??
48
????????????????????
????????11.5? (??6.7-20.8?)
Uhm JE, et al. 2009 WCLC.
49
??????????????????????
??,???? (1-2?) P0.027
P0.003
Uhm JE, et al. 2009 WCLC.
50
???????? Vs. ????
20
?????(?)
?????????????????? ???????2008???????????
51
??

• ????????????????,????????????????????????????????
  ??????????????
• ?????????????????????????????????,???????????????
  ??????????????????????????????
• ????????????,???????????????? ,???????,??????????

52

• ????

53
??????????????????????????
Response Rate
MST 7.4-10.3 Months
1YS 26 - 43
Data from prospective randomized phase III trials
with 4000 patients participated
54
?????????????????????? TKI
Trial Chemo Regimen RR() TTP (months) OS (months)
INTACT 1 GEM/CIS GEM/CIS/G250 GEM/CIS/G500 47.2 51.2 50.3 6 5.8 5.5 10.9 9.9 9.9
INTACT 2 CAR/PAC CAR/PAC/G250 CAR/PAC/G500 28.7 30.4 30 5 5.3 4.6 9.9 9.8 8.7
TALENT GEM/CIS GEM/CIS/E150 28.2 30 5.6 5.4 10.1 9.9
TRIBUTE CAR/PAC CAR/PAC/E150 19.3 21.5 4.9 5.1 10.6 10.8
Gandara DR et al, Clinical Lung Cancer 2006,
7(6) 385-388.
55
?????????????????????
Gatzemeier, U et al. J Clin Oncol
20072515451552.
56
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?????????? (46??)
??
CR/PR/SD

• ?????PD????????????
• ??????
• ??????
• ??????
• ?????????

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????????
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???NSCLC????,???????? ??????????????PFS?OS
64
SATURN????

• ????
• PFS in all patients
• PFS in EGFR IHC

????????????? ???,????,????????? ??????
F. Cappuzzo. et al, J Clin Oncol 277s, 2009
(suppl abstr 8001)
65
SATURN????????

• ??EGFR??????EGFR-TKI?????????????????????????????I
  II?????
• ????????2009?ASCO???????
• 29??????,152???????

F. Cappuzzo. et al, J Clin Oncol 277s, 2009
(suppl abstr 8001)
66
??????PFS IHC??
1.0 0.8 0.6 0.4 0.2 0
Erlotinib Placebo
PFS at 12 wks () 54 40
PFS at 24 wks () 32 18
HR0.69 (0.580.82) Log-rank plt0.0001
PFS probability
Erlotinib (n307)
Placebo (n311)
0 8 16 24 32 40 48 56 64 72 80 88 96
Time (weeks)
PFS???????????????6?????
F. Cappuzzo. et al, J Clin Oncol 277s, 2009
(suppl abstr 8001)
67
??? (ORR)
????(n436) ???(n445)
??? (CR/PR), 12 5
???? (SD), 48.6 45.4
????? (CRPRSD), 60.6 50.8 p0.0035
F. Cappuzzo. et al, J Clin Oncol 277s, 2009
(suppl abstr 8001)
68
SATURN??

• ??????????????????????????,???????,???????
• ??????????????,???29??????(Plt0.0001)
• ????????????? (12 vs.560.6 vs 50.8)
• ????????????,???????,???????
• ??????12??????????(40.8 vs 27.4)
• ??????????

F. Cappuzzo. et al, J Clin Oncol 277s, 2009
(suppl abstr 8001)
69
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