Concurrent and Consolidative Carboplatin Plus Nab-Paclitaxel or Paclitaxel in Locally Advanced NSCLC: A Multicenter, Randomized Clinical Trial.

Abstract

We investigated the efficacy and toxicity of thoracic radiation therapy (RT) plus concurrent and consolidation carboplatin with either solvent-based paclitaxel (sb-paclitaxel) or solvent-free nanoparticle albumin-bound paclitaxel (nab-paclitaxel). This multicenter phase 1/2 randomized trial included patients with inoperable stage IIIA/B nonsmall cell lung cancer (AJCC 7) and an Eastern Cooperative Oncology Group performance status of 0-1. In phase 1, 6 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 2, 92 patients were randomly assigned 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 2 cycles. Two phase 1 patients had dose-limiting toxicities, setting the phase 2 nab-paclitaxel dose at 40 mg/m². For the phase 2 cohort, 2-year overall survival was 67% for sb-paclitaxel and 56% for nab-paclitaxel (P = .10), with progression-free survival of 44% and 27%, respectively (P = .14). Fewer patients completed consolidation with nab-paclitaxel (26%) versus sb-paclitaxel (58%) (P = .005). Grade 3 and higher adverse events were more frequent with nab-paclitaxel (56%) than with sb-paclitaxel (30%) (P = .029). Nab-paclitaxel was associated with higher toxicity and numerically lower efficacy than sb-paclitaxel when used with thoracic radiation in locally advanced nonsmall cell lung cancer.