3200 - CTONG 1509 : Phase 3 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 < 0.001) (HR = 0.55,95%CI 0.41-0.75). The median PFS per investigator was 18.0 months (95% CI 15.2-20.7) in BE and 11.2 months (95%CI 9.7-12.5) in E (p < 0.001) (HR = 0.57,95% CI 0.44-0.75). The objective response rate by IRC in the BE and E groups was 86.3% and 84.7%, respectively (p = 0.741). The most common grade 3 or worse adverse events in BE group were hypertension, proteinuria and rash; and in the E alone group were rash, elevated alanine aminotransferase and elevated aspartate aminotransferase. Results for resistance biomarker analysis will be presented onsite.

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.