Comparative Efficacy and Safety of Erlotinib in Non-Small Cell Lung Cancer (NSCLC) of Squamous Cell and Adenocarcinoma Histology in the Phase III Ncic Ctg Br.21 and Saturn (BO18192) Trials

ABSTRACT Background Tumors of squamous cell (SC) histology are present in 25–30% of lung cancer patients (pts), and are more frequent in pts with a history of smoking. Erlotinib is an oral EGFR TKI shown to prolong progression-free survival (PFS) compared with placebo in first-line (1L) maintenance (SATURN; Cappuzzo, Lancet Oncol 2010) and second- or third-line (2L/3L) NSCLC settings (BR-21; Shepherd, NEJM 2005). Data from these pivotal studies were retrospectively analyzed to compare outcomes for pts with tumors of SC histology with those of pts diagnosed with adenocarcinomas (AD). Methods BR.21 randomized ECOG PS 0–3 pts with advanced NSCLC who progressed after 1L or 2L chemotherapy 2:1 to erlotinib (150 mg daily) or placebo. SATURN randomized ECOG PS 0–1 pts with advanced NSCLC who did not progress after 1L chemotherapy 1:1 to maintenance therapy with erlotinib (150 mg daily) or placebo. PFS and overall survival (OS) were estimated using Kaplan-Meier methods. Hazard ratios (HRs) were calculated using Cox regression analysis. Results 587 and 763 pts were evaluable in BR.21 and SATURN, respectively. A higher percentage of SC pts were smokers (current or ex-) and males versus AD pts in both studies. Most other baseline characteristics were similar between histology groups within each study. Efficacy and safety outcomes are shown (Table). In an interaction model analyzing for differential treatment effects on survival by SC and AD histology, P-values were >0.65 and >0.45 for PFS and OS in BR.21, respectively, and >0.2 for PFS in SATURN, providing no evidence for a statistically significant differential effect. Conclusions Analyses of data from two large pivotal trials associated erlotinib treatment with significant survival benefit in both SC and AD histology subgroups, supporting its efficacy in pts with SC NSCLC in the 1L maintenance, 2L, and 3L settings. Measure Placebo arm Erlotinib arm HR (95% CI) BR.21 (N = 587) Grade 3–5 adverse events, n (%) AD (n = 365) 75 (63) 148 (60) – SCC 56 (72) 109 (76) – Median PFS, mo AD 1.84 2.37 0.62 (0.49–0.79) SCC 1.81 2.27 0.48 (0.35–0.67) Median OS, mo AD 5.36 7.75 0.76 (0.58–0.98) SCC 3.58 5.57 0.60 (0.44–0.82) SATURN (N = 763) Grade 3–5 adverse events, n (%) AD (n = 403) 27 (14) 59 (29) – SCC (n = 360) 23 (12) 41 (25) – Median PFS, mo AD 2.60 2.83 0.63 (0.51–0.78) SCC 2.60 3.02 0.77 (0.61–0.96) Disclosure S. Wojtowicz-Praga: Dr. Wojtowicz-Praga is an employee of and holds stock options in Roche/Genentech. L. Leon: Dr. Leon is an employee of and holds stock options in Roche/Genentech.