Original ResearchWeekly 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
Section snippets
Evidence before this study
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Limited efficacy of systemic treatments for patients with advanced non–small-cell lung cancer (NSCLC) beyond first-line therapy
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Bevacizumab has activity in non-squamous NSCLC (nsNSCLC) and was approved in first-line therapy combined with chemotherapy by Food and Drug Administration (FDA) and European Medicines Agency (EMA)
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Bevacizumab add-on to weekly paclitaxel first-line therapy has almost doubled the response rate and the progression-free survival (PFS), with a favourable safety profile in
Background
During the last decades, new combined therapies have contributed to improve outcomes in patients with advanced NSCLC in the first-line setting. More recently, immune checkpoint inhibitors (ICIs) given alone or in combination with chemotherapy have been shown to prolong survival compared with chemotherapy given alone in selected patients [[1], [2], [3], [4], [5]]. However, the vast majority of patients experience further disease progression which requires subsequent therapy [6]. Drugs usually
Study design
This double-arm, randomised, open-label, multicentre, phase III clinical trial was conducted in patients with pre-treated advanced nsNSCLC. Patients were allowed to crossover to the other arm after disease progression over the study. This study was approved by a local ethics committee (CPP Nord-Ouest III, France) and complied with French legislation, Good Clinical Practices and the principles outlined in the latest version of the Declaration of Helsinki. After approvals, the study was
Patients' disposal and characteristics
A total of 166 randomised patients [wPAC-BEV group: 111 (67%), DOC group: 55 (33%)] were included between May 31, 2013 and August 13, 2014. Among this ITT population, two patients withdrew before their first wPAC-BEV cycle, leading to a safety population based on 164 patients (Fig. 1).
Patients' characteristics were balanced between treatment groups (Table 1). The majority of patients (69%) received only one previous line of chemotherapy and 31% had been previously exposed to bevacizumab
Discussion
Weekly paclitaxel combined with bevacizumab as second- or third-line therapy demonstrated superiority over docetaxel in terms of PFS, the primary end-point, with a 38% risk reduction in disease progression, and ORR (22·5% and 5·5%, respectively) in a population of patients with advanced nsNSCLC. No superiority of paclitaxel plus bevacizumab was observed on OS. However, the optional crossover design of the study may have impacted this result as more docetaxel-treated patients crossed over after
Contributors
The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Funding
The study is supported by Roche (supplying bevacizumab and unrestricted grant).
Role of the funding source
The study was sponsored by Intergroupe Francophone de Cancérologie Thoracique (IFCT). Roche (Boulogne Billancourt, France) supplied bevacizumab and a complementarygrant 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.
Conflict of interest statement
A.B.C. has reported receiveing honoraria from Roche, AstraZeneca, Bristol-Myers Squibb, BoehringerIngelheim, MSD, Novartis and Pfizer and travel grants from Roche, AstraZeneca, BoehringerIngelheim, Novartis and Pfizer. C.A.V. has reported receiving grants, personal fees and non-financial support from Roche. O.M. has received personal fees from BMS, BoehringerIngelheim, Astra Zeneca, Novartis and Hoffman-Roche. F.B. has received personal fees from Astra Zeneca, BMS, BoehringerIngelheim, Clovis
Acknowledgements
The authors thank AUXESIA (M-O. Barbaza) for writing and editing support.
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