CTONG 1509: Phase III Study of Bevacizumab with or Without Erlotinib in Untreated Chinese Patients with Advanced EGFR-mutated NSCLC

Background This study is an open-labeled, randomized, multicenter phase III study to investigate the efficacy and safety of bevacizumab (B) with or without erlotinib (E) in Chinese EGFR-mutated non-small cell lung cancer (NSCLC) patients (NCT02759614). Methods Patients with advanced non-squamous NSCLC harbouring EGFR-mutation were randomly (1:1) assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). Random assignment was stratified by sex (female/male), disease stage (stage IIIb vs. stage IV vs. recurrence), and EGFR gene mutation (exon 19 deletion vs. exon 21 L858R). The primary endpoint was Progression-free survival (PFS), as determined by an independent review committee (IRC). Secondary endpoints were PFS by investigator, tumor response (by IRC and investigator), overall survival (OS), time to failure (TTF), safety, patient-reported outcome (PRO) and exploratory biomarker analysis. Next-generation sequencing (NGS) of a 448-gene panel and transcriptome sequencing (RNA-Seq) was used for resistance biomarker analysis of paired frozen tissue samples. Results From Mar 31, 2016 to Jul 26, 2017, 311 patients from 14 centers across China were randomized to receive BE (N = 157) or E (N = 154). Median follow-up time was 22 months for BE and 21.5 months for E. Baseline characteristics were well balanced in each arm. The median PFS by IRC was 18.0 months (95% CI 15.2-20.7) in BE and 11.3 months (95%CI 9.8-13.8) in E (p Conclusions As compared with E alone, B plus E showed superior efficacy with acceptable tolerability. This regimen could be a new standard first-line regimen in EGFR mutated NSCLC. Clinical trial identification NCT02759614. Editorial acknowledgement Li Zhang, from Shanghai Roche Pharmaceuticals Ltd. Legal entity responsible for the study Guangdong Association of Clinical Trials (GACT). Funding Shanghai Roche Pharmaceuticals Ltd. Disclosure Q. Zhou: Honoraria (self): AstraZeneca; Honoraria (self): Roche. Y. Wu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim. All other authors have declared no conflicts of interest.