OncoTargets and Therapy (Nov 2016)
A randomized Phase II trial of the tumor vascular disrupting agent CA4P (fosbretabulin tromethamine) with carboplatin, paclitaxel, and bevacizumab in advanced nonsquamous non-small-cell lung cancer
Abstract
Edward B Garon,1,2 Jeffrey D Neidhart,3 Nashat Y Gabrail,4 Moacyr R de Oliveira,5 Jai Balkissoon,6 Fairooz Kabbinavar1,2 1Department of Medicine, 2Department of Hematology and Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, 3San Juan Oncology Associates, Farmington, NM, 4Gabrail Cancer Center, Canton, OH, 5Northwest Medical Specialties, Tacoma, WA, 6Global Product Development and Immuno-Oncology, PPD, Wilmington, NC, USA Introduction: Combretastatin A4-phosphate, fosbretabulin tromethamine (CA4P) is a vascular disrupting agent that targets tumor vasculature. This study evaluated the safety of CA4P when combined with carboplatin, paclitaxel, and bevacizumab in chemotherapy-naïve subjects with advanced nonsquamous, non-small-cell lung cancer. Methods: Adult subjects with confirmed American Joint Committee on Cancer six stage IIIB/IV non-small-cell lung cancer and an Eastern Cooperative Oncology Group performance score of 0 or 1 were randomized to receive six cycles (treatment phase) of paclitaxel (200 mg/m2), carboplatin (area under the concentration versus time curve 6), and bevacizumab (15 mg/kg) on day 1 and repeated every 21 days, or this regimen plus CA4P (60 mg/m2) on days 7, 14, and 21 of each cycle. Subjects could then receive additional maintenance treatment (excluding carboplatin and paclitaxel) for up to 1 year. Results: Sixty-three subjects were randomized, 31 to control and 32 to CA4P, and 19 (61.3%) and 17 (53.1%), respectively, completed the treatment phase. Exposure to study treatment and dose modifications were comparable between the randomized groups. The overall incidence of treatment-emergent adverse events was similar between groups, with increased neutropenia, leukopenia, and hypertension in the CA4P group. Deaths, serious adverse events, and early discontinuations from treatment were comparable between the randomized treatment groups. The overall tumor response rate with CA4P was 50% versus 32% in controls. Overall and progression-free survival rates were comparable between the groups. Conclusion: CA4P plus carboplatin, paclitaxel, and bevacizumab appears to be a tolerable regimen with an acceptable toxicity profile in subjects with advanced non-small-cell lung cancer. Keywords: CA4P, bevacizumab, paclitaxel, carboplatin, NSCLC
