2240 - Phase III study comparing bevacizumab plus erlotinib (BE) to erlotinib (E) in patients (pts) with untreated NSCLC harboring EGFR mutations: NEJ026

Background

Combinations of EGFR-TKIs and VEGF inhibitors are one of the candidates for next strategy for EGFR-mutated lung cancer. We conducted a phase III study comparing BE to E in pts with untreated non-small-cell lung cancer (NSCLC). This study includes the pts with central nervous system (CNS) metastases (mets).

Methods

Chemotherapy-naïve pts with advanced non-squamous NSCLC harboring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). Pts with asymptomatic stable CNS mets that did not require corticosteroids were allowed to enroll. The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. This study was planned to enroll 214 pts in total.

Results

Between Jun 3, 2015, and Aug 31, 2016, 228 pts with EGFR mutations were enrolled. There were one cessation prior to the study treatment and one withdrawal of consent; the remaining 226 pts were assigned to BE (n = 112) and E (n = 114). Pts were followed up for a median of 12.4 months. The interim analysis showed that the study met its primary endpoint. At data cutoff (Sept 21, 2017), median PFS was 16.9 months (95% CI 14.2-21.0) in BE and 13.3 months (11.1-15.3) in E (p = 0.0157) (HR 0.605, 95% CI 0.417-0.877). The number of pts with CNS mets at the enrollment was 72 (32.1%). In pts without CNS mets, median PFS was 18.0 months (95% CI 15.4- not reached) in BE and 15.1 months (11.1-16.1) in E (p = 0.0141). In pts with CNS mets, median PFS was 12.7 months (95% CI 9.8- 18.1) in BE and 11.2months (8.8-14.7) in E (p = 0.413). Although some toxicities such as hemorrhage, proteinuria, and hypertension significantly increased in BE compared to in E, there was no significant difference among other toxicities between BE and E. Five cases had low-grade pneumonitis in E but no pneumonitis in BE. There was no treatment-related death.

Conclusions

In this study, BE as a combination of EGFR-TKIs and VEGF inhibitors achieved durable response, especially absence of CNS mets. BE is a promising regimen for EGFR-mutated NSCLC.

Clinical trial identification

UMIN000017069.

Legal entity responsible for the study

North East Japan Study Group (NEJSG).

Funding

Chugai Pharmaceutical.

Editorial Acknowledgement

This study is supported by funding from Chugai pharmaceutical.

Disclosure

T. Fukuhara: Research funding: AstraZeneca, MSD, Ono, Bristol-Myers, Chugai, Novartis. S. Iwasawa: Speakers' bureau: Ono Pharmaceutical Co., Ltd, AstraZeneca K.K.; Research funding to institution: Teijin Pharma Limited, Ono Pharmaceutical Co., Ltd. O. Yamaguchi: Consulting or advisory role: AstraZeneca; Speakers' bureau: AstraZeneca, Bristol-Myers Squibb, Ono Pharmaceutical, Boehringer Ingelheim Japan. M. Okada, A. Gemma: Speakers' bureau, research funding: Chugai Company. K. Hagiwara: Honoraria: AstraZeneca, Ono Pharmaceutical; Patents, royalties, intellectual property: LSI Medience. T. Nukiwa: Consulting or advisory role: Asahi Kasei, Nippon Boehringer Ingelheim. S. Morita: Honoraria: Chugai. K. Kobayashi: Consulting or advisory role: AstraZeneca; Speakers bureau: Chugai, AstraZeneca, Ono, Eli Lilly. M. Maemondo: Research funding, lecture fee: Chugai Pharmaceutical. All other authors have declared no conflicts of interest.