晚期腸癌靶向治療進(jìn)展徐瑞華教授

1、主要內(nèi)容主要內(nèi)容 以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代的來(lái)臨以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代的來(lái)臨 多個(gè)靶向藥物聯(lián)合的重新定位多個(gè)靶向藥物聯(lián)合的重新定位 靶向藥物治療的廣泛研究靶向藥物治療的廣泛研究 ERBITUX in first-line treatment of mCRC Phase III CRYSTAL study: Study design Stratification factors: Region ECOG performance status Populations: Randomized patients (n=1217) Safety population (n=1202) IT

2、T population (n=1198) FOLFIRI Irinotecan (180 mg/m2) + 5-FU (400 mg/m2 bolus + 2400 mg/m2 as 46-h continuous infusion) + LV (every 2 weeks) ERBITUX + FOLFIRI ERBITUX (IV 400 mg/m2 on day 1, then 250 mg/m2 weekly) + irinotecan (180 mg/m2) + 5-FU (400 mg/m2 bolus + 2400 mg/m2 as 46-h continuous infusi

3、on) + LV (every 2 weeks) R EGFR-expressing mCRC Van Cutsem E, et al. ASCO 2007 (Abstract No. 4000) 1.0 0.8 0.9 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 02468101214161820 Primary endpoint: PFS (ITT population) PFS estimate Van Cutsem E, et al. ASCO 2007 (Abstract No. 4000) PFS time (months) 1-year PFS rate: 2

4、3% vs 34% FOLFIRI (n=599) ERBITUX + FOLFIRI (n=599) PFS ITT: HR=0.85; p=0.048 mPFS ERBITUX + FOLFIRI: 8.9 months mPFS FOLFIRI: 8.0 months Independent assessment of response Outcome FOLFIRI (n=599) (%) ERBITUX + FOLFIRI (n=599) (%) CR PR SD PD 0.3 38.4 46.7 9.0 0.5 46.4 37.4 8.8 ORR 95% CI 38.7 34.84

5、2.8 46.9 42.951.0 DCR 85.4 84.3 Van Cutsem E, et al. ECCO 2007 (Abstract No. 3001) 39% 47% Response rate (%) p=0.0038a aCochranMantelHaenszel test KRAS analysis: Objective and methodology To retrospectively investigate the impact of the KRAS mutation status of tumors on PFS and RR in the first-line

6、treatment of mCRC with FOLFIRI ERBITUX Efficacy analyses repeated on KRAS evaluable population Genomic DNA isolated from archived tumor material Paraffin-embedded, formalin-fixed tissue KRAS mutation status of codons 12/13 determined using quantitative PCR-based assay Van Cutsem E, et al. J Clin Onc

7、ol 2008;26 (Suppl. abstract 2) KRAS evaluable population 587 subjects analysed for KRAS mutation status 540 (45%) subjects: KRAS evaluable population 348 (64.4%) KRAS wild-type192 (35.6%) KRAS mutant 171 subjects with events (49.1%) Group A: 105 (54.7%)Group B: 87 (45.3%) 101 subjects with events (5

8、2.6%) 1198 subjects (ITT) Group A: 172 (49.4%)Group B: 176 (50.6%) FOLFIRIERBITUX + FOLFIRI Van Cutsem E, et al. J Clin Oncol 2008;26 (Suppl. abstract 2) Relating KRAS status to efficacy Primary endpoint: PFS KRAS wild-type 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 024681012141618 Months Progressi

9、on-free survival estimate ERBITUX + FOLFIRIFOLFIRI KRAS wild-type (n=348) HR=0.68; p=0.017 mPFS ERBITUX + FOLFIRI: 9.9 months mPFS FOLFIRI: 8.7 months 1-year PFS rate 25% vs 43% Van Cutsem E, et al. J Clin Oncol 2008;26 (Suppl. abstract 2) Relating KRAS status to efficacy Primary endpoint: PFS KRAS

10、mutant KRAS mutant (n=192) HR=1.07; p=0.75 mPFS ERBITUX + FOLFIRI: 7.6 months mPFS FOLFIRI: 8.1 months 0246810121416 Months ERBITUX + FOLFIRIFOLFIRI 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Progression-free survival estimate Van Cutsem E, et al. J Clin Oncol 2008;26 (Suppl. abstract 2) Relating K

11、RAS status to efficacy: PFS ERBITUX + FOLFIRI HR=0.63 (p=0.007) Median PFS: Wild-type (n=172) 9.9 months vs mutant (n=105) 7.6 months FOLFIRI HR=0.97 (p=0.87) Median PFS: Wild-type (n=176) 8.7 months vs mutant (n=87) 8.1 months 0.5 1.0 0.4 0.3 0.2 0.1 0.0 0.6 0.7 0.8 0.9 802461016 PFS estimate Time

12、(months) ERBITUX + FOLFIRI wild-type ERBITUX + FOLFIRI mutant 1214 0.5 1.0 0.4 0.3 0.2 0.1 0.0 0.6 0.7 0.8 0.9 Time (months) FOLFIRI wild-type FOLFIRI mutant 8024610161214 PFS estimate Van Cutsem E, et al. J Clin Oncol 2008;26 (Suppl. abstract 2) Relating KRAS status to efficacy Secondary endpoint:

13、Response p=0.0025a FOLFIRIERBITUX + FOLFIRI aCochran-Mantel-Haenszel (CMH) test KRAS wild-type (n=348)KRAS mutant (n=192) p=0.46a FOLFIRIERBITUX + FOLFIRI Van Cutsem E, et al. J Clin Oncol 2008;26 (Suppl. abstract 2) Relating KRAS status to outcome: Most common grade 3/4 adverse events KRAS wild-typ

14、eKRAS mutant Adverse events, % FOLFIRI (n=176) ERBITUX + FOLFIRI (n=173) FOLFIRI (n=87) ERBITUX + FOLFIRI (n=105) Any Neutropenia 50.6 16.5 78.0 25.4 55.2 23.0 72.4 21.9 Febrile neutropenia Diarrhea 0.6 9.1 0.6 17.3 0 12.6 3.8 13.3 Vomiting2.84.66.92.9 Fatigue4.52.32.39.5 Acne-like rasha016.2017.1 I

15、nfusion-related reactions 01.703.8 aThere was no grade 4 acne-like rash Van Cutsem E, et al. J Clin Oncol 2008;26 (Suppl. abstract 2) Conclusions: CRYSTAL study Adding ERBITUX to FOLFIRI in mCRC leads to a significant increase in PFS (HR=0.85; p=0.048) The benefit of ERBITUX + FOLFIRI is greater in

16、patients with KRAS wild-type tumors: PFS (HR=0.68; p=0.017) Response rate 59% vs 43% (p=0.0025) The grade 3/4 adverse-event profile was similar in the KRAS wild-type and mutant populations OPUS: Study design Primary endpoint Overall confirmed response rate (as assessed by independent review) Seconda

17、ry endpoints PFS time OS time Rate of curative surgery for metastases Safety ERBITUX + FOLFOX4a 400 mg/m2 initial IV infusion (day 1) then 250 mg/m2 weekly + oxaliplatin 85 mg/m2 + 5-FU/LV every 2 weeks FOLFOX4a Oxaliplatin 85 mg/m2 + 5-FU/LV every 2 weeks EGFR-detectable mCRC R Stratification by: E

18、COG PS 0/1, 2 Bokemeyer C, et al. J Clin Oncol 2008;26 (Suppl. abstract 4000) aTreatment until progression, symptomatic deterioration or unacceptable toxicity KRAS evaluable population 233 (69%) subjects: KRAS evaluable population 134 (58%) KRAS wild-type99 (42%) KRAS mutant Group A: 52 (53%)Group B

19、: 47 (47%) 337 subjects (ITT) Group A: 61 (46%)Group B: 73 (54%) FOLFOXERBITUX + FOLFOX Bokemeyer C, et al. J Clin Oncol 2008;26 (Suppl. abstract 4000) KRAS wild-type: n=134 (58%)KRAS mutant: n= 99 (42%) p=0.011 p=0.16 Role of KRAS status in response rate Bokemeyer C, et al. J Clin Oncol 2008;26 (Su

20、ppl. abstract 4000) 37 61 49 33 Relating KRAS status to efficacy Secondary endpoint: PFS KRAS wild-type 0.5 1.0 0.4 0.3 0.2 0.1 0.0 0.6 0.7 0.8 0.9 802461012 Months KRAS wild-type: HR=0.57; p=0.016 mPFS ERBITUX + FOLFOX: 7.7 months mPFS FOLFOX: 7.2 months Progression-free survival estimate FOLFOX ER

21、BITUX + FOLFOX Bokemeyer C, et al. J Clin Oncol 2008;26 (Suppl. abstract 4000) Relating KRAS status to efficacy Secondary endpoint: PFS KRAS mutant KRAS mutant HR=1.83; p=0.0192 mPFS ERBITUX + FOLFOX: 5.5 months mPFS FOLFOX: 8.6 months FOLFOX ERBITUX + FOLFOX 0.5 1.0 0.4 0.3 0.2 0.1 0.0 0.6 0.7 0.8

22、0.9 802461012 Months Progression-free survival estimate Bokemeyer C, et al. J Clin Oncol 2008;26 (Suppl. abstract 4000) Relating KRAS status to efficacy: Progression-free survival 0.5 1.0 0.4 0.3 0.2 0.1 0.0 0.6 0.7 0.8 0.9 802461012 PFS estimate Time (months) ERBITUX + FOLFOX wild-type ERBITUX + FO

23、LFOX mutant 0.5 1.0 0.4 0.3 0.2 0.1 0.0 0.6 0.7 0.8 0.9 802461012 Time (months) FOLFOX wild-type FOLFOX mutant ERBITUX + FOLFOX HR=0.45; p=0.0009 mPFS Cet + FOLFOX wild-type (n=61): 7.7 months mPFS Cet + FOLFOX mutant (n=52): 5.5 months FOLFOX HR=1.40; p=0.1655 mPFS FOLFOX wild-type (n=73): 7.2 mont

24、hs mPFS FOLFOX mutant (n=47): 8.6 months PFS estimate Bokemeyer C, et al. J Clin Oncol 2008;26 (Suppl. abstract 4000) Most common grade 3/4 AEs KRAS wild-typeKRAS mutant Adverse event, % FOLFOX (n=73) ERBITUX + FOLFOX (n=61) FOLFOX (n=47) ERBITUX + FOLFOX (n=52) Any Neutropenia Febrile neutropenia 6

25、3.0 32.9 1.4 83.6 41.0 0 78.7 44.7 4.3 67.3 25.0 0 Diarrhea5.511.512.85.8 Peripheral sensory neuropathy 8.24.92.13.8 Acne-like rasha014.8011.5 Infusion-related reactions 01.407.7 aThere was no grade 4 acne-like rash Bokemeyer C, et al. J Clin Oncol 2008;26 (Suppl. abstract 4000) Conclusions: OPUS st

26、udy The addition of ERBITUX to FOLFOX increased the response rate by 10% (46% vs 36%) In patients with KRAS wild-type tumors, addition of ERBITUX to FOLFOX resulted in a significant and relevant improvement in: Response rate (61% vs 37%; p=0.011) PFS (HR=0.57; p=0.016) 1. Van Cutsem E, et al. J Clin

27、 Oncol 2008;26 (Abstract No. 2); 2. Bokemeyer C, et al. J Clin Oncol 2008;26 (Abstract No. 4000) ERBITUX + CT in KRAS wild-type: Consistent results Response rate (%) 59 37 0 10 20 30 40 50 60 70 CRYSTAL1 (n=348) OPUS2 (n=134) 43 61 FOLFIRIFOLFOXERBITUX + FOLFIRI ERBITUX + FOLF0X CRYSTALKRAS wild-typ

28、e: HR=0.68 p=0.017 32% risk reduction for progression OPUSKRAS wild-type: HR=0.57 p=0.016 43% risk reduction for progression 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 024681012141618 Time (months) PFS estimate 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 024681012 Time (months) PFS estimate ERBITUX

29、 in pretreated mCRC Evidence of correlation between KRAS wild-type and EGFR inhibitor efficacy in chemorefractory CRC: Response Reference Treatment No. of patients (wild-type: mutant) Objective response, n (%) Wild-typeMutant Livre A, et al. (J Clin Oncol 2008) ERBITUX CT114 (78:36) 34 (44) 0 (0) Be

30、nvenuti S, et al. (Cancer Res 2007) Panitumumab or ERBITUX or ERBITUX + CT 48 (32:16) 10 (31) 1 (6) DeRoock W, VanCutsem E, Tejpar S et al. (Ann Onc 2008) ERBITUX or ERBITUX + irinotecan 113 (67:46) 27 (41) 0 (0) Finocchiaro G et al. (ASCO Proceedings 2007) ERBITUX CT81 (49:32) 13 (26) 2 (6) Di Fior

31、e F et al. (Br J Cancer 2007) ERBITUX + CT59 (43:16) 12 (28) 0 (0) Khambata-Ford S et al. (J Clin Oncol 2007) ERBITUX80 (50:30) 5 (10) 0 (0) Amado R, Van Cutsem E et al. (J Clin Oncol 2008) Panitumumab208 (124:84) 21 (17) 0 (0) NCIC CTG CO.17 Karapetis C, et al. WCGIC 2008 June 28 10:45 Session XVII

32、 Role of KRAS mutations in predicting response, progression-free survival and overall survival in irinotecan-refractory patients treated with cetuximab plus irinotecan for a metastatic colorectal cancer: Analysis of 281 individual data from published series Abstract O-018 World Congress GI Cancer Ba

33、rcelona 2008 Di Fiore F (1), Van Cutsem E (1), Laurent-Puig P (2), Siena S (3), Frattini M (4), De Roock W (1), Lievre A (2), Sartore-Bianchi A (3), Bardelli A (5), Tejpar S (1) (1) Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven- Belgium; (2) Institut National de la Sant et de la

34、Recherche Mdicale U775, Universit Paris-Descartes, Paris- France; (3) Divisione Oncologia Medica Falck, Ospedale Niguarda Ca Granda, Milan- Italy; (4) Institute Of Pathology, Locarno- Switzerland; (5) Laboratory of Molecular Genetics Institute for Cancer Research and Treatment, University of Torino

35、Medical School, Torino- Italy ResponsenKRAS mutation (n)KRAS WT (n) Complete response (CR)30 (0)3 (1.6) Partial response (PR)740 (0)74 (40.6) Stable disease (SD)10741 (41.4) 66 (36.3) Progressive disease (PD) 9758 (58.6)39 (21.5) Response to cetuximab-Irinotecan according to KRAS status (n=281) Di F

36、iore F, Van Cutsem E et al, WCGIC Barcelona, Ann Oncol, 2008 abstract O-018 Meta-analysis in chemorefractory CRC 6 Meta-analysis in chemorefractory CRC PFS according to KRAS status Di Fiore F, Van Cutsem E et al, WCGIC Barcelona, Ann Oncol, 2008 abstract O-018 Meta-analysis in chemorefractory CRC OS

37、 according to KRAS status Di Fiore F, Van Cutsem E et al, WCGIC Barcelona, Ann Oncol, 2008 abstract O-018 Overall survival according to KRAS mutation and skin toxicity Time (months) 1.00 0.75 0.50 0.25 0.00 0102030 p=0.0008 15.6 months (95% CI: 10.922) 10.7 months (95% CI: 8.316.3) 5.6 months (95%CI

38、: 2.810.6) Survival probability 2 good prognostic factors (wild-type and grade 2/3 skin toxicity) 0 good prognostic factors (KRAS mutant and grade 0/1 skin toxicity) 1 good prognostic factor (wild-type or grade 2/3 skin toxicity) Livre A, et al. J Clin Oncol 2008 NCIC CO.17: randomized phase III tri

39、al EGFR testing by IHC Disease progression or Unacceptable toxicity Stratification: Center ECOG PS (0 or 1 vs 2) R E G I S T E R R A N D O M I Z E 1:1 ERBITUX + BSC BSC alone Failed or intolerant to all recommended therapies Jonker D, et al. N Engl J Med 2008 ERBITUX + BSC CENSORED BSC CENSORED Subj

40、ects at risk ERBITUX+BSC 2872171367837144000 BSC285197854426128210 Proportion alive 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Months 0369121518212427 HR 0.77 (95% CI: 0.64, 0.92) Stratified log-rank p=0.0046 Study armMS95% CI ERBITUX + BSC6.1 months5.4, 6.7 BSC alone4.6 months4.2, 4.9 Jonker D, et a

41、l. N Engl J Med 2008 NCIC CTG CO.17: Overall Survival ERBITUX + BSC CENSORED BSC CENSORED Proportion progression-free 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Months 03691215 HR 0.68 (95% CI: 0.570.80) Stratified log-rank p10m Conclusions KRAS is the first molecular marker used to select a targeted

42、 therapy in combination with a standard chemotherapy regimen ERBITUX brings a new era of tailored therapy to treatment of mCRC ERBITUX in combination with a standard first-line treatment for patients with mCRC is an important new option in patients with KRAS wild-type tumors 主要內(nèi)容主要內(nèi)容 以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代

43、的來(lái)臨以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代的來(lái)臨 多個(gè)靶向藥物聯(lián)合的重新定位多個(gè)靶向藥物聯(lián)合的重新定位 靶向藥物治療的廣泛研究靶向藥物治療的廣泛研究 Interim results from PACCE irinotecan + bevacizumab panitumumab for first-line treatment of mCRC study design Hecht J, et al. Abstract 279 S C R E E N I N G R A N D O M I Z E Ox-based CT (e.g. FOLFOX) N=800 inv choice In-based C

44、T (e.g. FOLFIRI) N=200 inv choice Panitumumab 6mg/kg Q2W Ox-CT Bevacizumab Panitumumab 6 mg/kg Q2W Iri-CT Bevacizumab Ox-CT Bevacizumab Iri-CT Bevacizumab 1:1 1:1 Interim results from PACCE irinotecan + bevacizumab +/- panitumumab for first-line treatment of mCRC median PFS (central review) Hecht J,

45、 et al. Abstract 279 100 80 60 40 20 0 PFS (%) 0510152025 Time (days) Panitumumab + Bevacizumab/Iri-CT Bevacizumab/Iri-CT *PFS events (%)Median (95% CI months 54 (47)10.1 (8.213.1) 43 (37)11.1 (9.013.2) HR = 1.2 (95% CI: 0.801.82)* *Descriptive only BACK Interim results from PACCE irinotecan + bevac

46、izumab panitumumab for first-line treatment of mCRC response by KRAS status Hecht J, et al. Abstract 279 N Pmab+Bev/iri-CT n/N (%) Bev/iri-CT n/N (%) Odds ratio (95% CI) Wild-type KRAS 115 31/57 (54)27/58 (47)1.42 (0.633.21) Mutant KRAS 85 14/46 (30)15/39 (38)0.59 (0.231.55) BACK 0510152025 Interim

47、results from PACCE oxaliplatin + bevacizumab +/- panitumumab for first-line treatment of mCRC PFS (central review) Hecht JR, et al. Abstract 273 100 80 60 40 20 0 PFS events (%) Median (95% CI) months pmab+bev/Ox-CT599.6 (8.810.9) bev/Ox-CT5211.1 (10.311.9) HR=1.27 (95% CI: 1.051.53)* *Descriptive o

48、nly Time (months) PFS (%) BACK Surviving (%) Interim results from PACCE oxaliplatin + bevacizumab +/- panitumumab for first-line treatment of mCRC OS (central review) Hecht JR, et al. Abstract 273 06121824 100 80 60 40 20 0 Time (months) Death events n(%) Median (95% CI), months pmab+bev/Ox-CT143 (3

49、5)19.4 (18.420.8 bev/Ox-CT108 (26)NE HR=1.43 (95% CI: 1.111.83)* *Descriptive only. Statistical significance is limited by the lack of a prespecified significance boundary Interim results from PACCE oxaliplatin + bevacizumab +/- panitumumab for first-line treatment of mCRC OS by age Hecht JR, et al.

50、 Abstract 273 100 80 60 40 20 00 6121824 Time (months) Age 80 years 100 80 60 40 20 00 6121824 Time (months) Age 80 years bev/Ox-CT pmab+bev/Ox-CT Surviving (%) Surviving (%) BACK Interim results from PACCE oxaliplatin + bevacizumab +/- panitumumab for first-line treatment of mCRC response rates (ce

51、ntral review) Hecht JR, et al. Abstract 273 Tumour response, n (%) Pmab + bev/OX-CT (N = 413) Bev/OX-CT (N=410) Best ORR187 (45)189 (46) Complete response0 (0) 2 (1) Partial response187 (45)189 (46) Stable disease121 (29)138 (34) Progressive diseaseb28 (7)17 (4) Not done or unevaluablec 78 (19)64 (1

52、6) BACK Metastatic CRC Trial: CAIRO 2 750 Previously untreated patients PFS +3 months Arm B： XELOX + Bevacizumab + Cetuximab Arm A: XELOX + Bevacizumab CAIRO 2: Results Arm A: Chemo + Bev Arm B: Chemo + Bev + C225 CAIRO 2: TTP CAIRO 2: Overall Survival CAIRO 2: Toxicities 小小 結(jié)結(jié) 聯(lián)合聯(lián)合Bevacizumab與抗與抗EG

53、FR抗體一線(xiàn)治療晚期抗體一線(xiàn)治療晚期 CRC的臨床研究結(jié)果中，未能顯示協(xié)同的作用的臨床研究結(jié)果中，未能顯示協(xié)同的作用 聯(lián)合聯(lián)合Bevacizumab與抗與抗EGFR抗體的治療毒性有抗體的治療毒性有 所增加所增加 如何進(jìn)行多個(gè)靶點(diǎn)藥物聯(lián)合的臨床試驗(yàn)提出了挑如何進(jìn)行多個(gè)靶點(diǎn)藥物聯(lián)合的臨床試驗(yàn)提出了挑 戰(zhàn)。戰(zhàn)。理論理論 結(jié)果結(jié)果 主要內(nèi)容主要內(nèi)容 以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代的來(lái)臨以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代的來(lái)臨 多個(gè)靶向藥物聯(lián)合的重新定位多個(gè)靶向藥物聯(lián)合的重新定位 靶向藥物治療的廣泛研究靶向藥物治療的廣泛研究 Targeting Agents in CRC Bevacizumab VEGF

54、Traps AZD2171 Sonafinib Sunitinib mTOR inhibitor Cell Cycle Inhibitors Leonard B. Saltz,et al. JCO, 2007 標(biāo)準(zhǔn)治療失敗后的轉(zhuǎn)移性結(jié)直腸標(biāo)準(zhǔn)治療失敗后的轉(zhuǎn)移性結(jié)直腸 癌應(yīng)用舒尼替尼治療的癌應(yīng)用舒尼替尼治療的IIII期研究期研究 舒尼替尼的最好臨床有效率舒尼替尼的最好臨床有效率 無(wú)貝伐單抗組無(wú)貝伐單抗組 貝伐單抗組貝伐單抗組 所有病例所有病例 （n=40） （n=42） （n=82） 療效療效 病例數(shù)病例數(shù) % 病例數(shù)病例數(shù) % 病例數(shù)病例數(shù) % 部分緩解部分緩解 0 0 1 2.4 1 1.2

55、 穩(wěn)定穩(wěn)定 14 35.0 10 23.8 24 29.3 穩(wěn)定穩(wěn)定22周周 11 27.5 2 48 13 15.9 有效性：舒尼替尼治療后，病灶大小變化有效性：舒尼替尼治療后，病灶大小變化 情況（同治療前大小比較）情況（同治療前大小比較） PFS and OS in Sutent treatment 小結(jié)小結(jié)：Sunitib單藥對(duì)晚期單藥對(duì)晚期CRC的有效性低，但應(yīng)用化療的有效性低，但應(yīng)用化療 聯(lián)合聯(lián)合Sunitinib在在CRC中的臨床研究值得開(kāi)展中的臨床研究值得開(kāi)展 主要內(nèi)容主要內(nèi)容 以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代的來(lái)臨以分子指標(biāo)為指導(dǎo)的靶向治療時(shí)代的來(lái)臨 多個(gè)靶向藥物聯(lián)合的重新定位多個(gè)靶向藥物聯(lián)合的重新定位 靶向藥物治療的廣泛研究靶向藥物治療的廣泛研究 Independent assessment of response Outcome FOLFIRI (n=599) (%) ERBITUX + FOLFIRI (n=599) (%) CR PR SD PD 0.3 38.4 46.7 9.0 0.5 46.4 37.4 8.8 ORR 95% CI 38.7 34.842.8 46.9 42.951.0 DCR 85.4 84.3 Van