1、Slideset on:Thatcher N,Hirsch FR,Luft AV,et al.Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer(SQUIRE):an open-label,randomized,controlled phase 3 trial.Lancet Oncol.2015;16:763-774.
2、SQUIRE:Improved Survival With Necitumumab+Gemcitabine/Cisplatin vs Gemcitabine/Cisplatin as First-line Treatment in Patients With Squamous NSCLC This activity is supported by educational grants from Genentech,Lilly,and Novartis Pharmaceuticals Corporation.About These Slides Users are encouraged to u
3、se these slides in their own noncommercial presentations,but we ask that content and attribution not be changed.Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care Options (email )Disclaimer The materials published on the Clin
4、ical Care Options Web site reflect the views of the authors of the CCO material,not those of Clinical Care Options,LLC,the CME providers,or the companies providing educational grants.The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States
5、Food and Drug Administration.A qualified healthcare professional should be consulted before using any therapeutic product discussed.Readers should verify all information and data before treating patients or using any therapies described in these materials.Background:Necitumumab in Advanced Squamous
6、NSCLC Platinum-based doublet chemotherapy longtime standard first-line treatment option for the 30%of pts with squamous NSCLC1 Necitumumab:fully human IgG1 antiEGFR mAb Addition to gemcitabine/cisplatin increased antitumor activity in mouse xenograft models of NSCLC2 Failed to improve OS when added
7、to pemetrexed/cisplatin in pts with advanced nonsquamous NSCLC in phase III INSPIRE trial3 Phase III SQUIRE trial evaluated safety,efficacy of necitumumab+gemcitabine/cisplatin vs gemcitabine/cisplatin in chemotherapy-naive pts with stage IV squamous NSCLC1 1.Thatcher N,et al.Lancet Oncol.2015;16:76
8、3-774.2.Samakoglu S,et al.Cancer Genomic Proteomics.2012;9:77-92.3.Paz-Ares L,et al.Lancet Oncol.2015;16:328-337.Slide credit: SQUIRE:Phase III Study Schema Primary endpoint:OS(ITT)Secondary endpoints:PFS,ORR,TTF,safety Thatcher N,et al.Lancet Oncol.2015;16:763-774.Stratified by ECOG PS(0-1 vs 2)and
9、 geographic region (North America/Europe/Australia vs South America/South Africa/India vs eastern Asia)Chemotherapy-naive pts with stage IV squamous NSCLC,ECOG PS 0-2,adequate organ function(N=1093)Slide credit: Necitumumab 800 mg IV on Days 1,8+Gemcitabine 1250 mg/m2 IV on Days 1,8+Cisplatin 75 mg/
10、m2 IV on Day 1 Q3W(n=545)Gemcitabine 1250 mg/m2 IV on Days 1,8+Cisplatin 75 mg/m2 IV on Day 1 Q3W (n=548)Maximum 6 cycles Pts without PD receiving necitumumab could continue on single-agent necitumumab until PD or unacceptable toxicity PD OS significantly improved with necitumumab+gemcitabine/cispla
11、tin vs gemcitabine/cisplatin alone SQUIRE:OS Thatcher N,et al.Lancet Oncol.2015;16:763-774.Slide credit: 0 20 40 60 80 100 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 Mos OS(%)N+G/C Censored pts G/C Censored pts N+G/C(n=545)G/C(n=548)HR:0.84(95%CI:0.74-0.96;P=.01)Median OS,Mos(95%CI)11
12、.5(10.4-12.6)9.9(8.9-11.1)1-Yr OS,%(95%CI)48(43-52)43(39-47)2-Yr OS,%(95%CI)20(16-24)17(13-20)Necitumumab+Gemcitabine/Cisplatin,n/Events Gemcitabine/Cisplatin,n/Events HR(95%CI)Age group,yrs 65 65 to 70 70 332/258 105/79 108/81 340/277 111/94 97/71 0.88(0.74-1.04)0.63(0.46-0.85)1.03(0.75-1.42)Sex Wo
13、men Men 95/77 450/341 90/72 458/370 0.88(0.64-1.21)0.84(0.73-0.98)Race White Non-white 457/355 88/63 456/369 92/73 0.86(0.75-1.00)0.78(0.55-1.09)Smoking status Never/light exsmoker Current smoker 44/34 500/383 53/44 495/398 0.82(0.52-1.29)0.85(0.74-0.98)ECOG PS 0 1 2 164/117 332/260 49/41 180/139 32
14、0/261 47/42 0.82(0.64-1.05)0.85(0.72-1.01)0.78(0.51-1.21)Overall ITT population 545/418 548/442 0.84(0.74-0.96)SQUIRE:OS by Subgroup Slide credit: 0.45 1.5 1 Favors necitumumab plus gem/cisplatin Favors gem/cisplatin Thatcher N,et al.Lancet Oncol.2015;16:763-774.SQUIRE:PFS PFS significantly improved
15、 with necitumumab+gemcitabine/cisplatin vs gemcitabine/cisplatin alone Median TTF:4.3 vs 3.6 mos,respectively(P=.006)Thatcher N,et al.Lancet Oncol.2015;16:763-774.Slide credit: HR:0.85(95%CI:0.74-0.98;P=.02)Median PFS,Mos(95%CI)5.7(5.6-6.0)5.5(4.8-5.6)3-Mo PFS,%(95%CI)79(76-83)73(68-76)6-Mo PFS,%(95
16、%CI)45(40-49)37(33-42)N+G/C(n=545)G/C(n=548)0 20 40 60 80 100 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 Mos PFS(%)N+G/C Censored pts G/C Censored pts SQUIRE:Responses ORR similar between 2 groups,but disease control was more common with the addition of necitumumab(P=.043)Slide credit: Thatcher N,et al.Lancet Oncol.2015;16:763-774.Response,%Necitumumab+Gemcitabine/Cisplatin (n=545)Gemcitabine/Cisplatin (n=548)ORR,%(95%CI)CR PR 31(27-35)0 31 29(25-33)1 28 SD 51 48 PD 8 10 DCR,%(95%CI)82(78-