FDA Approval Insights: Ramucirumab/Erlotinib in EGFR+ Metastatic NSCLC

Welcome to a very special edition of OncLive^® On Air! I’m your host today, Caroline Seymour.

OncLive^® On Air is a podcast from OncLive, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

Today, we had the pleasure of speaking with Edgardo S. Santos, MD, a medical oncologist at Florida Precision Oncology, and a clinical affiliate associate professor at the Charles E. Schmidt College of Medicine at Florida Atlantic University, to discuss the recent FDA approval of ramucirumab (Cyramza) and erlotinib (Tarceva) in EGFR-mutant metastatic non–small cell lung cancer.

On May 30, 2020, the FDA approved the combination as a frontline treatment for patients with metastatic non–small cell lung cancer whose tumors harbor EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

The approval is based on findings from the phase 3 RELAY trial, in which patients were randomized to receive erlotinib at 150 mg daily in combination with either ramucirumab at 10 mg/kg every 2 weeks or placebo. Patients received treatment until disease progression or unacceptable toxicity.

At a median follow-up of 20.7 months, the investigator-assessed median progression-free survival (PFS) with the combination was 19.4 months versus 12.4 months with erlotinib alone, translating to a 41% reduction in the risk of progression or death with the addition of ramucirumab.

Patients who harbored exon 19 deletions experienced a median PFS of 19.6 months with the combination versus 12.5 months with erlotinib alone. Patients with exon 21 L858R mutations had a PFS of 19.4 months versus 11.2 months with the combination versus erlotinib alone, respectively.

At a data cutoff date of December 31, 2019, the updated hazard ratio for overall survival was 0.92.

In terms of safety, the rate of grade 3 or higher adverse events (AEs) was 72% with the combination versus 54% with erlotinib alone. The rate of serious AEs was 29% and 21%, respectively.

In total, 13% of patients in the combination arm versus 11% of those in the erlotinib-alone arm discontinued treatment due to treatment-related AEs. Additionally, 85% versus 71% of patients required dose reductions due to these events, respectively.

In our exclusive interview, Santos, discussed the data that led to the approval of the combination and shared his thoughts on its utility in the frontline setting.