AvaALL: Open-label randomized phase IIIb trial evaluating the efficacy and safety of standard of care with or without continuous bevacizumab (BV) treatment beyond disease progression in patients (pts) with advanced nonsquamous non-small cell lung cancer (NSCLC) after first-line (1L) treatment with BV plus platinum-doublet chemotherapy (CT).

Abstract

TPS7612 Background: Pts with NSCLC have a poor prognosis upon progression following 1L CT. Although the disease may have progressed on 1L CT, it is likely still dependent on VEGF-mediated pathways. Thus, persistent VEGF suppression along with second- and third-line cytotoxic regimens may yield clinical benefit. Analyses have associated this strategy with improved survival in NSCLC (Nadler et al, Oncologist 2011) and mCRC (Grothey et al JCO 2008). Methods: AvaALL (MO22097; NCT01351415), a multicenter (144 centers, 20 countries) open-label randomized (1:1) 2-arm phase IIIb study, recruits pts with advanced non-squamous NSCLC that has progressed after 1L treatment with BV plus a platinum-doublet and at least 2 cycles of BV maintenance monotherapy. Pts in the experimental arm receive BV at the same dose from induction (7.5 or 15 mg/kg IV on D1 of every 21-day cycle) continuously along subsequent lines, plus investigator’s choice of second-line agent (limited to pemetrexed, docetaxel, or erlotinib) and subsequent lines of treatment. Pts in the control arm receive investigator’s choice of agent alone in second and subsequent lines of treatment, but no further BV treatment. Stratifications include nature of second-line standard treatment, number of cycles of BV maintenance (≤6 vs. >6) and smoking status. The primary endpoint is overall survival (OS). Secondary endpoints include 6-, 12-, and 18-month OS rates, progression-free survival, time to progression at second and third progressive disease (PD), response rate, disease control rate, duration of response at second and third PD, and safety of BV across multiple lines of treatment. Exploratory objectives include quality of life assessment through multiple treatment lines, and biomarker analysis. Assuming a median OS beyond PD of 7.9 months in the control group and 10.1 months in the treatment arm (HR 0.78), 528 events are required to achieve 80% power for the log-rank test at a 2-sided significance level of 5%. Enrollment began in June 2011.