Ramucirumab Extends Survival in Advanced NSCLC

Results from the phase III REVEL study show that ramucirumab (Cyramza; Lilly Oncology), in combination with docetaxel, prolongs overall survival (OS) for patients with relapsed stage IV non–small cell lung cancer (NSCLC). The trial's results were presented by Maurice Pérol, MD, head of thoracic oncology at the Cancer Research Center of Lyon in France, during the American Society of Clinical Oncology's Annual Meeting in Chicago, IL, May 30–June 3.

FDA-approved second-line agents for refractory NSCLC include docetaxel, pemetrexed (Alimta; Lilly Oncology), and erlotinib (Tarceva; Roche). However, patients taking these agents have a median OS of about 7 to 9 months, and only about 10% experience tumor shrinkage.

Ramucirumab is a fully humanized monoclonal antibody that binds to VEGFR-2, a main driver of angiogenesis in tumors, and acts as an antagonist by blocking the VEGFR-2 ligands VEGF-A, VEGF-C, and VEGF-D. At present, it is FDA-approved only as second-line therapy for advanced gastric cancer. Pérol noted that it is the first agent in about a decade to improve the outcome of NSCLC patients in the second-line setting, compared to chemotherapy alone.

The REVEL study included 1,253 participants with stage IV NSCLC, of which 74% were non-squamous, the most common subtype. All had disease progression after platinum-based chemotherapy and were randomized to receive either ramucirumab plus docetaxel or placebo plus docetaxel. The median OS with ramucirumab was 10.5 months (compared with 9.1 months for placebo), and the median progression-free survival was 4.5 months (compared with 3.0 months for placebo). Tumor shrinkage occurred in 22.9% of patients who received ramucirumab, versus 13.6% of those who received the placebo. These effects were consistent across both non-squamous and squamous subtypes.

“It's one reason REVEL's data are encouraging,” said Gregory Masters, MD, a lung cancer specialist at the Helen F. Graham Cancer Center in Newark, DE, “because the squamous subtype of NSCLC, where KRAS mutations are frequent, is otherwise not yet druggable.”

No new ramucirumab-related safety concerns were identified with REVEL, and the drug's main side effect, hypertension, was readily manageable. Pérol concluded that as second-line therapy for NSCLC, the benefit–risk balance of combining ramucirumab with docetaxel is favorable.

“It's exciting to have another agent that shows activity against this difficult-to-treat disease,” added Masters.