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Weekly Paclitaxel Plus Bevacizumab versus Docetaxel As Second- or Third-Line Treatment in Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC): Results of the IFCT-1103 ULTIMATE Study
37 Pages Posted: 29 Jun 2019
More...Abstract
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 3 trial, patients with advanced nsNSCLC treated with one or two prior lines, including one platinum-based doublet, were centrally randomised to receive paclitaxel 90 mg/m² (D1, D8, D15) plus bevacizumab 10 mg/kg (D1, D15) every 28 days or docetaxel (75 mg/m²) every 21 days; crossover was allowed after disease progression. Primary endpoint was progression-free survival (PFS).
Results: Between May 2013 and August 2014, 166 patients were randomized (paclitaxel plus bevacizumab: 111, docetaxel: 55). Median PFS was longer in paclitaxel plus bevacizumab patients than in docetaxel patients [5·4 months vs 3·9 months, adjusted hazard ratio (HR) 0·61 (95% CI 0·44-0·86); p=0·005]. Objective response rates (ORR) were respectively 22·5% (95% CI 14·8-30·3) and 5·5% (95% CI 0·0-11·5) (p=0·006). Median overall survivals were similar (adjusted HR 1·17; p=0·50). Crossover occurred in 21/55 (38·2%) docetaxel-treated patients. Grade 3-4 adverse events were reported in 45·9% and 54·5% of patients treated with paclitaxel and bevacizumab or docetaxel, respectively (p=NS), including neutropenia (19·3% vs 45·4%), neuropathy (8·3% vs 0·0%), and hypertension (7·3% vs 0·0%). Three patients died due to treatment-related adverse events (1·8% in each group).
Conclusion: Weekly paclitaxel plus bevacizumab as second- or third-line improves PFS and ORR compared to docetaxel in nsNSCLC patients, with an acceptable safety profile. These results place weekly paclitaxel plus bevacizumab as a valid option in this population.
Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT01763671.
Funding Statement: The study was sponsored by IFCT. Roche (Boulogne Billancourt, France) supplied bevacizumab, and a complementary grant but had no role in the study design, conduct of the study, and data analysis and had no other involvement in the study. The study was also supported by the French National Cancer Institute (INCa) and French League Against Cancer.
Declaration of Interests: ABC has received honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Novartis, Pfizer, and travel grants from Roche, AstraZeneca, Boehringer Ingelheim, Novartis and Pfizer. CAV has declared grants, personal fees and non-financial support from Roche. OM has declared personal fees from BMS, Boehringer Ingelheim, Astra Zeneca, Novartis, ans Hoffman-Roche. FB has declared personal fees from Astra Zeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, Hoffman-Roche, Novartis, Merck, MSD, Pierre Fabre and Pfizer. GZ has declared grant from Roche and BMS, personal fees from Roche, BMS, Astra Zeneca, and MSD, and non-financial support from BMS, Astra Zeneca and Pfizer. DP has declared has declared personal fees from Roche Hoffman, Astellas, Lilly, Janssen, BMS, Merck, Astra Zeneca, Novartis, Sanofi and Pfizer. CFD has declared other from MSD (CPLF 2017), Laidet Medical (ERS 2016), and Boehringer Ingelheim (CPLF 2016). EP has declared personal fees and non-financial support from Astra Zeneca, BMS and personal fees from Pfizer. DMS has declared personal fees from Roche, BMS, MSD and Eli Lilly. BB has received institutional grants for clinical and translational research from AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, Pfizer, Roche-Genentech, Sanofi-Aventis, Clovis, GSK, Servier, EOS, Onxeo, OncoMed, Inivata, OSE Pharma.
Ethics Approval Statement: This study was approved by a local Ethic Committee (CPP Nord-Ouest III, France), and complied with French legislation, Good Clinical Practices, and the principles outlined in the latest version of Declaration of Helsinki. After approvals, the study was implemented in 36 hospitals and cancer centres in France.
Keywords: NSCLC, paclitaxel, docetaxel, bevacizumab
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