Long survival of never smoking non-small cell lung cancer (NSCLC) patients (pts) treated with erlotinib HCl (OSI-774) and chemotherapy: Sub-group analysis of TRIBUTE

Abstract

7061 Background: Erlotinib (Tarceva) is a potent HER1/EGFR tyrosine kinase inhibitor (TKI). Monotherapy trials of EGFR-TKIs have suggested never smokers and pts with bronchioloalveolar cell carcinoma (Shah, Proc ASCO 2003 #2524; Miller, Proc ASCO 2003 #2491) are more likely to benefit from these agents. TRIBUTE was a placebo-controlled study randomizing pts with previously untreated advanced NSCLC to receive erlotinib, 150 mg/d, or placebo (PBO) with 6 cycles of carboplatin/paclitaxel (CP) followed by maintenance monotherapy. Methods: Pts with performance status (PS) of 0 or 1 were eligible. Randomization was stratified by stage, >5% weight loss (WL) prior 6 mos., measurable disease (MD), and study site. The primary endpoint was overall survival (OS). Other endpoints included time to progression (TTP), objective response (OR) and duration of response. Results: 1059 pts randomized/treated (526 erlotinib; 533 PBO). No difference was observed in OS (p=0.95), OR (p=0.36) or TTP (p=0.36) with erlotinib and CP vs CP alone. Univariate analyses with pre-specified factors at entry (stage, WL, MD, age, gender, race, smoking hx, PS, EGFR status and histology) were used to see if any were predictive of OS. Smoking history as recorded on Case Report Forms was available on all pts in the intent-to-treat analysis. Pts who reported never smoking in the erlotinib arm (n=69) had an improved OS versus never smoking pts who received CP alone (n=44) (median survival 23 versus 10 months; HR 0.49 95%CI 0.28–0.85). This subgroup was well-balanced for known prognostic features between the 2 arms. None of the other factors were predictive for OS. Conclusions: Although erlotinib with CP did not confer an advantage in OS over CP alone in all enrolled NSCLC pts, the addition of erlotinib to CP markedly prolonged survival in pts who reported never smoking. This latter observation is consistent with results of prior studies of EGFR-TKIs and warrants confirmation in a randomized trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech; OSI Pharmaceuticals, Inc. Genentech AstraZeneca; Genentech Genentech