CCO-Lung-Fellows-Thatcher-LO-鳞癌课件

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.SQUIRE: Improved Survival With Necitumumab + Gemcitabine/Cisplatin vs Gemcitabine/Cisplatin as First-line Treatment in Patients With Squamous NSCLCThis activity is supported by educational grants from Genentech, Lilly, and Novartis Pharmaceuticals Corporation.第一页，共十四页。About These Slides Users are encouraged to use 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 Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care Options (email )DisclaimerThe materials published on the Clinical Care Options Web site reflect the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 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.第二页，共十四页。Background: Necitumumab in Advanced Squamous NSCLCPlatinum-based doublet chemotherapy longtime standard first-line treatment option for the 30% of pts with squamous NSCLC1Necitumumab: fully human IgG1 antiEGFR mAb Addition to gemcitabine/cisplatin increased antitumor activity in mouse xenograft models of NSCLC2Failed to improve OS when added to pemetrexed/cisplatin in pts with advanced nonsquamous NSCLC in phase III INSPIRE trial3Phase III SQUIRE trial evaluated safety, efficacy of necitumumab + gemcitabine/cisplatin vs gemcitabine/cisplatin in chemotherapy-naive pts with stage IV squamous NSCLC11. Thatcher N, et al. Lancet Oncol. 2015;16:763-774.2. 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: 第三页，共十四页。SQUIRE: Phase III Study SchemaPrimary endpoint: OS (ITT)Secondary endpoints: PFS, ORR, TTF, safetyThatcher N, et al. Lancet Oncol. 2015;16:763-774.Stratified by ECOG PS (0-1 vs 2) and 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/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 cyclesPts without PD receiving necitumumab could continue on single-agent necitumumab until PD or unacceptable toxicityPD第四页，共十四页。OS significantly improved with necitumumab + gemcitabine/cisplatin vs gemcitabine/cisplatin aloneSQUIRE: OSThatcher N, et al. Lancet Oncol. 2015;16:763-774.Slide credit: 0204060801000246810 1214 1618 2022 2426 2830 32 3436 38 40MosOS (%)N + G/CCensored ptsG/CCensored ptsN + G/C (n = 545)G/C (n = 548)HR: 0.84 (95% CI: 0.74-0.96;P = .01)Median OS,Mos (95% CI)11.5 (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)第五页，共十四页。Necitumumab + Gemcitabine/ Cisplatin, n/EventsGemcitabine/ Cisplatin, n/EventsHR (95% CI)Age group, yrs 65 65 to 70 70332/258105/79108/81340/277111/9497/710.88 (0.74-1.04)0.63 (0.46-0.85)1.03 (0.75-1.42)SexWomenMen95/77450/34190/72458/3700.88 (0.64-1.21)0.84 (0.73-0.98)RaceWhiteNon-white457/35588/63456/36992/730.86 (0.75-1.00)0.78 (0.55-1.09)Smoking statusNever/light exsmokerCurrent smoker44/34500/38353/44495/3980.82 (0.52-1.29)0.85 (0.74-0.98)ECOG PS012164/117332/26049/41180/139320/26147/420.82 (0.64-1.05)0.85 (0.72-1.01)0.78 (0.51-1.21)Overall ITT population545/418548/4420.84 (0.74-0.96)SQUIRE: OS by SubgroupSlide credit: 0.451.51Favors necitumumab plus gem/cisplatinFavors gem/cisplatinThatcher N, et al. Lancet Oncol. 2015;16:763-774.第六页，共十四页。SQUIRE: PFSPFS significantly improved with necitumumab + gemcitabine/cisplatin vs gemcitabine/cisplatin aloneMedian 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% CI)45 (40-49)37 (33-42)N + G/C (n = 545)G/C (n = 548)0204060801000246810121416182022242628303234MosPFS (%)N + G/CCensored ptsG/CCensored pts第七页，共十四页。SQUIRE: ResponsesORR 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)CRPR31 (27-35)03129 (25-33) 128SD5148PD810DCR, % (95% CI)82 (78-85)77 (73-80)Not evaluable 12Not assessed1011第八页，共十四页。SQUIRE: Efficacy by EGFR ExpressionEGFR expression not predictive or prognostic of survival benefit Trend toward improved OS with high EGFR expression Slide credit: Thatcher N, et al. Lancet Oncol. 2015;16:763-774.Outcome, HR (95% CI)High EGFR Expression* (n = 374)Low EGFR Expression* (n = 608)Interaction P ValueOS0.75 (0.60-0.94)0.90 (0.75-1.07).24PFS0.88 (0.70-1.11)0.83 (0.69-0.99).68ORR0.97 (0.62-1.50)1.27 (0.90-1.79).34*EGFR expression determined in 982 pts with evaluable samples via IHC assay with EGFR PharmDx Kit (Dako) and independently scored by 2 pathologists. High: H-score 200; low: H-score 200.第九页，共十四页。Treatment-Related AEs of Interest, %Necitumumab + Gemcitabine/Cisplatin (n = 538)Gemcitabine/Cisplatin (n = 541)Any GradeGrade 3Any GradeGrade 3Any99729862Skin reactionsRash7976871210 1 1NeutropeniaFebrile neutropenia44124 1462281Fatigue437437Anemia42114611Hypomagnesemia319161Thrombocytopenia22102711Diarrhea162112Venous thromboembolic events9553Conjunctivitis7 120Arterial thromboembolic events5442Hypersensitivity/infusion rxn1 120Interstitial Lung disease1 1 1 1SQUIRE: Most Common AEsSlide credit: Thatcher N, et al. Lancet Oncol. 2015;16:763-774.第十页，共十四页。Conclusions and Faculty AssessmentNecitumumab addition to gemcitabine/cisplatin conferred significant survival benefit to chemotherapy-naive pts with stage IV squamous NSCLC vs gemcitabine/cisplatin alone Median OS: 11.5 vs 9.9 mos (P = .01)Median PFS: 5.7 vs 5.5 mos (P = .02)Grade 3 and serious AEs more common with necitumumab + gemcitabine/cisplatin vs gemcitabine/cisplatin (72% vs 62% and 48% vs 38%, respectively)Necitumumab plus gemcitabine/cisplatin approved by FDA for firstline treatment of patients with metastatic squamous NSCLCSlide credit: Thatcher N, et al. Lancet Oncol. 2015;16:763-774.第十一页，共十四页。Conclusions and Faculty AssessmentEGFR expression not predictive/prognostic of necitumumab benefitWeaknesses of this study: Dichotomous categorization of EGFR expression into high vs low groups may have reduced ability to detect efficacy differences Interpretation of subgroup analyses limited by size of subgroups Future directions: Explore benefit of continued necitumumab use following treatment with necitumumab + platinum-based doublet chemotherapy in squamous NSCLCSlide credit: Thatcher N, et al. Lancet Oncol. 2015;16:763-774.第十二页，共十四页。Go Online for More CCO Coverage of Immunotherapy!Downloadable resource summarizing current treatment of NSCLCDownloadable slidesets of key dataA CME-certified text module on immunotherapy with expert faculty commentary on key studies credit: 。(N = 1093)。(n = 548)。N + G/C。HR (95% CI)。P = .02)。(n = 541)。