Phase II trial of carboplatin, abraxane, and bevacizumab in NSCLC.

Abstract

e18016 Background: The addition of bevacizumab to carboplatin and paclitaxel has been shown to improve survival. Abraxane (nab-paclitaxel) may yield higher response rates than paclitaxel in NSCLC. This Phase II study was designed to investigate the combination of carboplatin (C), nab-paclitaxel (N-P), and bevacizumab (B) in first-line treatment of advanced NSCLC. Pharmacodynamic blood and imaging studies were performed to better understand the mechanism of action of bevacizumab both alone and in combination with chemotherapy and to assess biomarkers of response. Methods: Pts with previously untreated, non-squamous, advanced NSCLC were enrolled in an open-label Phase II trial. All patients were given a single induction dose of B 15 mg/kg on day -14. On day 1 combination therapy started with C AUC 6 d1, N-P 100 mg/m2 d 1, 8, 15, and B 15 mg/kg d1, on a 21 day cycle. Correlative imaging and biomarker studies were performed with FDG-PET, perfusion CT, and blood for circulating cellular and molecular biomarkers, on days -14 and -2 (prior to and 12 days after induction B), and every two cycles during treatment. Planned enrollment was 36. Changes in biomarkers from day -14 to day -2 were tested using the exact paired Wilcoxon test, and correlations with best percent difference in RECIST measurements of response were tested using the Kendall’s tau test. Results: Twenty-five pts have been enrolled thus far. Four pts came off study prior to first restaging; one for painful bony disease requiring radiation and three for toxicity (perforated diverticulitis, LFT abnormalities, and nausea/vomiting). One pt is currently in cycle 1; another pt dropped out before receiving any study drug. Of 19 pts evaluable for response to date, best response was 8 PR, 9 SD, and 2 PD. Induction B treatment was associated with statistically significant increases in levels of VEGF, PIGF, and SDF1a, and decrease in sVEGFR-1 levels. Blood flow and permeability decreased from baseline to day -2. Conclusions: Disease control rate (PR + SD) with combination therapy with C, N-P, and B was 74% (17/23). Pharmacodynamic blood and imaging biomarker studies in bevacizumab-treated NSCLC patients are feasible.