Overall survival (OS) in ATLAS, a phase IIIb trial comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy (chemo) with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC).

Abstract

7526 Background: The ATLAS study (n=768) was designed to evaluate B (15 mg/kg q3w)+ E (150 mg qd) vs. B + placebo (PL) following B + platin-containing doublet chemo in patients (pts) with stage IIIb/IV NSCLC. The trial met its primary (1°) endpoint of improving PFS. Median PFS was 4.8 mo for B + E vs. 3.7 mo for B + PL (HR=0.72, 95% CI: 0.59–0.88, p=0.0012). The safety profile for B + E was consistent with known profiles for B and E. Here we report on OS, a secondary endpoint. Methods: Enrolled pts were B-eligible (including pts with treated brain metastases and pts receiving low MW heparins); peripheral and/or extrathoracic squamous tumors allowed. Pts received 4 cycles of B (15 mg/kg q3w) + platinum-containing doublet chemo. Pts who did not progress after 4 cycles of B + chemo and had no significant toxicity were randomized to receive B + E or B + PL as maintenance therapy. OS was defined as time from randomization to death. The study was not powered to detect OS difference. The 1° OS analysis was prespecified to occur at the time of primary PFS analysis (July 18, 2009 cutoff). At the time of primary OS analysis, few death events had occurred (31% of pts had died). Two post-hoc analyses of OS, after more death events had occurred, were performed (data cutoffs, January 28 and June 19, 2009). Results: See Table. An equal percentage (39.7%) of patients in the B + E and B + PL arms received subsequent therapy with an EGFR tyrosine kinase inhibitor. Conclusions: For pts treated in the first-line setting for locally advanced, recurrent, or metastatic NSCLC, the addition of E to B after chemotherapy significantly improved PFS and may also provide OS benefit. Clinical and biomarker subset data will be presented. Data Cutoff Patients with events n/N (%) Median OS (mo) B+E vs. B HR (95% CI) p value July 18, 2008 (prespecified) 228/743 (31) 14.4 vs. 13.3 0.92 (0.70–1.21) 0.5604 January 28, 2009 357/768* (46) 14.4 vs. 13.6 0.90 (0.73–1.12) 0.3574 June 19, 2009 439/768* (57) 15.9 vs. 13.9 0.90 (0.74–1.09) 0.2686 * 25 pts were randomized after cutoff for main analysis of PFS. ** HR and p value based on prespecified, stratified analysis. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech AstraZeneca, Boehringer Ingelheim, Genentech, KEW Group (Diagnostics), Millennium, Pfizer, Roche Celgene, Roche Genentech, Roche Genzyme