Concurrent and consolidative carboplatin plus nab-paclitaxel or paclitaxel in locally advanced NSCLC A multicenter, randomized clinical trial.

Abstract

Introduction: We investigated the efficacy and toxicity of thoracic radiotherapy (RT) plus concurrent and consolidation carboplatin with either solvent-based paclitaxel (sb-Paclitaxel) or solvent-free, nanoparticle albumin-bound paclitaxel (nab-Paclitaxel).

Methods: This multicenter, phase I/II randomized trial included patients with inoperable stage IIIA/B NSCLC (AJCC 7) and an ECOG performance status of 0-1. In phase I, six patients received weekly nab-paclitaxel (50 mg/m²) and carboplatin (AUC 2) with concurrent thoracic RT (60 Gy in 30 fractions), followed by nab-paclitaxel (100 mg/m²) on days 1, 8, and 15 and carboplatin (AUC 6) on day 1 for two 21-day cycles. In phase II, 92 patients were randomized to weekly sb-paclitaxel (50 mg/m²) or nab-paclitaxel (40 mg/m²) with concurrent RT, followed by consolidation therapy with sb-paclitaxel or nab-paclitaxel and carboplatin for two cycles.

Results: Two phase I patients had dose-limiting toxicities, setting the phase II nab-paclitaxel dose at 40 mg/m². For the phase II cohort, two-year overall survival was 67% for sb-paclitaxel and 56% for nab-paclitaxel (P=0.10), with progression-free survival (PFS) of 44% and 27%, respectively (P=0.14). Fewer patients completed consolidation with nab-paclitaxel (26%) versus sb-paclitaxel (58%) (P=0.005). Grade 3 and higher adverse events were more frequent with nab-paclitaxel (56%) than with sb-paclitaxel (30%) (p=.0.029) CONCLUSIONS: Nab-paclitaxel was associated with higher toxicity and numerically lower efficacy than sb-paclitaxel when used with thoracic radiation in locally advanced NSCLC.