進行非小細胞肺がんにおいて生存に関する有益性が軽度認められた（Abstract: LBA8006）

Findings from the REVEL phase III study of patients with stage IV non-small cell lung cancer (NSCLC) indicate that a combination of a new anti-angiogenesis drug, ramucirumab, and standard docetaxel chemotherapy extends overall survival for patients who have a relapse after initial treatment compared to docetaxel plus placebo. The median overall survival was 10.5 months in the ramucirumab arm compared to 9.1 months in the placebo arm.   The late breaking study was presented at ASCO's 2014 Annual Meeting.

This phase III clinical trial marks the first time in a decade that a survival benefit has been achieved in second-line therapy for patients with advanced non-small cell lung cancer.

"This is the first treatment in approximately a decade to improve the outcome of patients in the second-line setting," said lead study author Maurice Pérol, M.D., Head of Thoracic Oncology at Cancer Research Center of Lyon in France. "The survival improvement is significant because patients with advanced NSCLC typically have a very short survival time following second-line therapy."

Ramucirumab is a monoclonal antibody that specifically targets VEGF receptor 2, blocking growth of new blood vessels in the tumor. No other approved anti-angiogenesis drugs are available in the second-line setting for advanced NSCLC, and currently ramucirumab is approved only for advanced gastric cancer treatment.
There is a large unmet medical need in the second-line treatment of advanced NSCLC, as all patients eventually experience a relapse following initial therapy. Approved second-line therapies for advanced NSCLC include docetaxel, erlotinib, and pemetrexed (for non-squamous NSCLC only), though clinical outcomes remain poor, with tumor shrinkage rates around 10 percent and median overall survival ranging between seven and nine months.

In the study, 1,253 patients with stage IV NSCLC (26 percent had the squamous subtype) that had progressed despite standard platinum-based therapy were randomly assigned to treatment with ramucirumab plus docetaxel or placebo plus docetaxel.

The addition of ramucirumab improved the efficacy of second-line docetaxel therapy – 22.9 percent of patients experienced tumor shrinkage in the ramucirumab arm compared to 13.6 percent in the placebo arm. The median overall and progression-free survival periods were 10.5 and 4.5 months in the ramucirumab plus docetaxel arm vs. 9.1 and 3 months in the placebo plus docetaxel arm, respectively. The survival benefits were consistent in the major subgroups of patients, including squamous and non-squamous subtypes, suggesting that this therapy could be suitable for all major subtypes of NSCLC. The safety profile was as expected for an anti-VEGFR agent in combination with docetaxel, with no increase in the rate of pulmonary hemorrhage.

"This study expands the treatment options for patients with recurrent or refractory non-small cell lung cancer," said Gregory A. Masters, M.D., ASCO Expert. "Ramucirumab is an effective targeted agent when added to chemotherapy, with low toxicity. This will be a significant benefit to those patients whose cancer progresses following initial chemotherapy."

This research was supported by ImClone, a wholly owned subsidiary of Eli Lilly.