Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer.

Introduction: Bevacizumab (B) improves survival of patients with metastatic, nonsquamous non-small cell lung cancer. Based on encouraging results from preclinical studies combining B with sunitinib (S), a phase II, randomized, open-label study (Study Assessing the Blockade of both VEGF Receptor and ligand to enhance Efficacy in Lung) was initiated to assess clinical outcomes of adding S to paclitaxel (P)/carboplatin (C) + B (PCB) for first-line treatment of locally advanced, metastatic, or recurrent nonsquamous non-small cell lung cancer.

Methods: Study enrollment was to occur in three phases. In the first phase, patients received PC + B (15 mg/kg every 3 weeks), +/-S (25 mg daily, 2 weeks on, 1 week off). If tolerated, the second phase would include a third cohort receiving 37.5 mg S. The third phase would consist of PCB +/- highest tolerable dose S.

Results: Between March 2007 and January 2008, 26 patients were randomized to receive PCB and 30 to PCB + S 25 mg. Because of poor tolerability, none of the patients were escalated to 37.5 mg S. Median treatment duration was 10.3 weeks for PCB and 6.0 weeks for PCB + S. Thirty-five percent of patients on PCB + S required S dose reduction, 52% required S treatment interruption, and 59% discontinued S because of adverse events, most frequently hematologic events (neutropenia, thrombocytopenia, and leukopenia) and fatigue. Patients receiving PCB + S required more B interruptions (38% versus 19% for PCB) and discontinuation (52% versus 35%) because of adverse events. Survival data were limited by small sample sizes and limited treatment duration. Overall survival was not mature at time of analysis: median 6.6 months for PCB + S and not reached for PCB. Two out of 25 efficacy-evaluable patients randomized to the PCB + S cohort had confirmed partial responses, compared with 5 of 19 randomized to the PCB cohort.

Conclusions: The addition of S to PCB was not well tolerated because of toxicities. This combination should not be studied further at these doses and schedules.