Phase II trial of nanoparticle albumin-bound paclitaxel, carboplatin, and bevacizumab in first-line patients with advanced nonsquamous non-small cell lung cancer.

Introduction: Carboplatin/paclitaxel chemotherapy with bevacizumab is an accepted standard treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). The development of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has circumvented many of the infusion difficulties associated with standard solvent-based paclitaxel (in Cremophor) and offers theoretical advantages in efficacy. This trial evaluated the combination of nab-paclitaxel, carboplatin, and bevacizumab in advanced (stage IIIB/IV) nonsquamous NSCLC.

Methods: Fifty patients with stage IIIB/IV NSCLC were enrolled between October 2005 and April 2006; 48 were treated with nab-paclitaxel 300 mg/m2, carboplatin area under the curve = 6, and bevacizumab 15 mg/kg every 21 days until progression or intolerable toxicity, up to 4 cycles; an additional 2 cycles could be administered to responding patients and the physician's discretion; maintenance bevacizumab was not administered. Patient demographics included: 56% female, median age 67 years (range, 32-83), performance status 0 (52%) or 1 (48%), adenocarcinoma 86%, and stage IV disease 82%. Responding patients received a minimum of 4 cycles. The primary end point was response rate.

Results: Response rate was 31% with a stable disease rate of 54%. No complete responses were observed. Median progression-free survival was 9.8 months (range, <1-22.3), and median survival was 16.8 months. Most frequent grades 3 and 4 treatment-related toxicities were neutropenia (54%) and fatigue (17%).

Conclusions: The combination of nab-paclitaxel, carboplatin, and bevacizumab was well tolerated with moderate neutropenia. Adverse events were manageable. Survival results are encouraging. These results indicate that this combination has promising activity as first-line therapy in patients with nonsquamous NSCLC.