Docetaxel Plus Ramucirumab Improves Outcomes in Advanced NSCLC

The addition of ramucirumab to docetaxel improved outcomes over placebo with docetaxel as a second-line treatment of patients with advanced non-small-cell lung cancer (NSCLC), according to results of the REVEL trial presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

“Despite advancements in genomics and identification of predictive biomarkers such as EGFR mutations or ALK rearrangement, there is still no… targeted therapy for the majority of patients with squamous and non-squamous carcinoma,” said Maurice Pérol, MD, of the Cancer Research Center of Lyon in France. Ramucirumab specifically targets VEGFR-2 and inhibits angiogenesis, and it has been shown to improve outcomes in gastric cancer as monotherapy.

In the phase III REVEL trial, 1,253 patients were randomized to either ramucirumab and docetaxel or placebo and docetaxel. A total of 1,245 actually received the assigned therapies and were included in the safety analysis.

The objective response rate was 22.9% for the ramucirumab group and 13.6% in the placebo group (P < .001). When stable disease was included along with complete and partial responses, the rate was 64% vs. 52.6% (P < .001). The median progression-free survival was 4.5 months for ramucirumab and 3 months for placebo, for a hazard ratio of 0.762 (95% CI, 0.677-0.859; P < .0001).

Most patients discontinued the study drug because of progressive disease, and went on to other therapies. The median overall survival (OS) was also better with ramucirumab, at 10.5 months vs. 9.1 months and an HR of 0.857 (95% CI, 0.751-0.979; P = .0235).

Pérol said the safety profile was as expected. There were some grade 3/4 adverse events (AEs) that were more common with ramucirumab, including neutropenia (48.8% vs 39.8%). There was also more grade 1/2 bleeding/hemorrhage with the study drug (26.5% vs 12.9%). There was no difference in AEs leading to death.

“REVEL is the first study… demonstrating a significant improvement of OS over chemotherapy in second-line treatment of patients with advanced NSCLC,” Pérol said. “Therefore, this combination represents a new therapeutic option for patients with good performance status and for patients eligible for an anti-angiogenic treatment in the second-line setting.”

Julie R. Brahmer, MD, of the Sidney Kimmel Comprehensive Cancer Center at John Hopkins University in Baltimore, was the discussant for the session and agreed that the results are positive and promising. It is important to note, however, that this was still a modest benefit with ramucirumab. “This is the first VEGF inhibitor to show benefit for squamous cell carcinoma patients,” she said, and added that more information is still needed on patients who received prior VEGF targeted therapies.