Ramucirumab Improves Overall Survival in Patients with Non-Small Cell Lung Cancer

Chicago—Patients with advanced, progressive non-small cell lung cancer (NSCLC) who received ramucirumab plus docetaxel had a significant improvement in overall survival and progression-free survival compared with a group taking docetaxel and placebo, according to a large, randomized, double-blind, placebo-controlled, phase 3 study.

Ramucirumab, an investigational agent administered via intravenous infusion, reduced the risk of death by 14% (hazard ratio [HR], 0.857; P=.0235) and increased overall survival by 1.4 months from 9.1 months in the placebo group to 10.5 months in the ramucirumab group. The drug also reduced the risk of disease progression by 24% (HR, 0.762; P<.0001) and increased the median progression-free survival by 1.5 months from 3.0 months in the placebo group to 4.5 months in the ramucirumab group.

Maurice Perol, MD, the study’s lead author and head of thoracic oncology at the Cancer Research Center of Lyon in France, said this was the first time that a drug significantly improved overall survival compared with chemotherapy alone in the second-line NSCLC setting. Dr. Perol, who presented the data on Saturday during a news conference at the ASCO meeting, said the magnitude of benefit was consistent across the majority of sub-groups, including patients with squamous and non-squamous carcinoma. ImClone, a wholly owned subsidiary of Eli Lilly Co., supported the study.

In April, the FDA approved ramucirumab to treat patients with advanced stomach cancer and granted the medication an orphan drug designation. Ramucirumab is a vascular endothelial growth factor receptor 2 antagonist.

In the REVEL trial, researchers examined the use of ramucirumab and docetaxel compared with placebo and docetaxel in more than 1200 patients in 26 countries who had NSCLC. ImClone, the manufacturer of ramucirumab, announced in a news release in February that it planned on submitting the data from the REVEL trial to regulatory authorities later this year.

Lung cancer is the leading cause of cancer death in the United States and is responsible for more deaths the combination of breast cancer, colon cancer, and prostate cancer. NSCLC accounts for approximately 85% of all lung cancer cases.

Dr. Perol noted chemotherapy was the standard of care as second-line therapy for patients with NSCLC who had disease progression after first-line treatment. Only 3 drugs (docetaxel, pemetrexed, and erlotinib) are approved in this setting, and median overall survival ranges from 7 to 9 months, according to Dr. Perol. He added that no trials have demonstrated an improvement in overall survival among patients with NSCLC who received a new agent plus standard second-line chemotherapy.

“There is a large unmet medical need in this setting,” Dr. Perol said.

This study included patients with stage IV, squamous or nonsquamous NSCLC whose disease progressed during or after a prior platinum-based chemotherapy with or without maintenance therapy. Patients were allowed to have previously received bevacizumab, and they were required to have an Eastern Cooperative Oncology Group performance status score of 1 or greater. They were randomized in a 1:1 ratio to receive 10 mg/kg of ramucirumab once every 3 weeks plus 75 mg/m³ of docetaxel once every 3 weeks or 10 mg/kg of placebo once every 3 weeks plus 75 mg/m³ of docetaxel once every 3 weeks.

The following grade 3 or higher adverse events were found in more than 5% of patients who received ramucirumab plus docetaxel: neutropenia, febrile neutropenia, fatigue, leukopenia, hypertension, and pneumonia. Dr. Perol said the rates of treatment-emergent adverse events leading to death (5.4% in the ramucirumab group versus 5.7% in the placebo group) and pulmonary hemorrhage (2.1% versus 1.6%) were similar between the groups.

—Tim Casey