Weekly paclitaxel plus bevacizumab versus docetaxel as second- or third-line treatment in advanced non-squamous non-small-cell lung cancer: Results of the IFCT-1103 ULTIMATE study.

PURPOSE: Second-line chemotherapy regimens have demonstrated poor benefit after failure of platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer (nsNSCLC). METHODS: In this multicentre, open-label phase III trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive 90 mg/m(2) of paclitaxel (D1, D8, D15) plus 10 mg/kg of bevacizumab (D1, D15) every 28 days or docetaxel (75 mg/m(2)) every 21 days; crossover was allowed after disease progression. Primary end-point was progression-free survival (PFS). ClinicalTrials.gov registration number: NCT01763671. RESULTS: One hundred sixty six patients were randomised (paclitaxel plus bevacizumab: 111, docetaxel: 55). The median PFS was longer in patients receiving paclitaxel plus bevacizumab than in patients receveing docetaxel [5.4 months versus 3.9 months, adjusted hazard ratio (HR) 0.61 (95% confidence interval [CI]: 0.44-0.86); p = 0.005]. Objective response rates (ORRs) were 22.5% (95% CI: 14.8-30.3) and 5.5% (95% CI: 0.0-11.5) (p = 0.006), respectively. Median overall survivals were similar (adjusted HR 1.17; p = 0.50). Crossover occurred in 21 of 55 (38.2%) docetaxel-treated patients. Grade III-IV adverse events (AEs) were reported in 45.9% and 54.5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p = NS), including neutropenia (19.3% versus 45.4%), neuropathy (8.3% versus 0.0%) and hypertension (7.3% versus 0.0%). Three patients died due to treatment-related AEs (1.8% in each group). CONCLUSION: Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared with docetaxel in patients with nsNSCLC, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01763671.