Squire: a Randomized, Multicenter, Open-Label, Phase III Study of Gemcitabine-Cisplatin (Gc) Chemotherapy Plus Necitumumab (Imc-11F8/Ly3012211) Vs Gc Alone in the First-Line Treatment of Patients (Pts) with Stage Iv Squamous Non-Small Cell Lung Cancer (Sq-Nsclc): Update on Key Subgroups

Aim: EGFR is detectable in most pts with sq-NSCLC tumors. Efficacy and safety of necitumumab (N), a human IgG1 anti-EGFR monoclonal antibody that inhibits ligand-binding and receptor activation, were evaluated in pts with advanced sq-NSCLC tumors. Methods: Pts with stage IV sq-NSCLC were randomized 1:1 to GC (G = 1250 mg/m2 iv, days 1 and 8; C = 75 mg/m2 iv, day 1) plus N (800 mg iv, days 1 and 8) (GC + N arm), or GC alone (GC arm) every 21 days for up to 6 cycles. GC + N pts with no progression continued on N alone until progressive disease or intolerable toxicity. The primary endpoint was overall survival (OS). Progression-free survival and safety were secondary endpoints. Subgroup analyses, evaluating efficacy by age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), gender, and race, were also performed. Planned sample size was 1080 pts, with 90% power and a 2-sided alpha level of 0.05. ClinicalTrials.gov identifier: NCT00981058. Results: 1093 pts were randomized. Baseline characteristics, exposure to chemotherapy, and post-progression anticancer therapy were similar between GC + N and GC arms. The table shows key OS results. The addition of N to GC statistically significantly improved OS (HR = 0.84, p = 0.012), and the safety profile of GC + N was acceptable across subgroups. OS Results N mOS, GC + N* N mOS, GC* HR† ITT population 545 11.5 548 9.9 0.84 Subgroups Age, y 520 11.5 529 9.9 0.84 ≥75 25 10.3 19 7.4 0.98 ECOG PS 0 164 13.8 180 12.9 0.82 1 332 10.7 320 9.2 0.85 2 49 9.5 47 6.9 0.78 Gender Female 95 13.0 90 11.4 0.88 Male 450 11.1 458 9.7 0.84 Race Caucasian 457 11.4 456 9.7 0.86 Non-Caucasian 88 12.6 92 11.8 0.78 mOS = median overall survival. *Data = median (months) estimated by the Kaplan-Meier method. †HR Conclusions: This study met its primary endpoint. GC + N demonstrated improved OS, with an acceptable safety profile, across all subgroups. Disclosure: M.A. Socinski: Steering Committee; L. Paz-Ares: I have provided scientific advice asn received honararium from Lilly; M. Reck: Member of advisory boards (compensated): Lilly, Hoffmann-La Roche, BMS, AstraZeneca, Pfizer, Boehringer Ingelheim, Novartis; K. Park: Advisory Board; Eli Lilly; F.R. Hirsch: Research funding (through University of Colorado) from ImClone - Lilly. Participated in steering committee for the study and advisory borad for Lilly – ImClone; H. Depenbrock: Lilly Employee S. Nanda: I am a lilly employee and I have stock ownership; N. Chouaki: I am a Lilly Employee, I have stock ownership; N. Thatcher: Honoraria :Advsiory Board and Speaker Bureau Member Lilly Imclone. All other authors have declared no conflicts of interest.