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ASCO 2014: Second-Line Treatment With Ramucirumab Plus Standard Docetaxel Extends Overall Survival in Advanced Lung Cancer

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Key Points

  • Ramucirumab plus docetaxel extended overall survival in patients with stage IV NSCLC who relapsed after initial platinum-based therapy.
  • The addition of ramucirumab reduced the risk of death by 14% and prolonged median overall survival by 1.4 months (10.5 months with ramucirumab vs 9.1 months with placebo).
  • Ramucirumab reduced the risk of progression by 24%, prolonging progression-free survival by 1.5 months (from 3.0 to 4.5 months), and increasing response rates from 13.6% to 22.9%.

Patients with stage IV non–small cell lung cancer (NSCLC) who relapsed after initial platinum-based therapy experienced extended overall survival with a combination of the antiangiogenic agent ramucirumab (Cyramza) and standard chemotherapy with docetaxel, compared to patients receiving docetaxel plus placebo in the phase III REVEL study. The median overall survival was 10.5 months in the ramucirumab group compared to 9.1 months in the placebo group. Results were presented at the 2014 ASCO Annual Meeting in Chicago (Abstract LBA8006^).

“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, MD, 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.”

Targeting the VEGF Receptor

Ramucirumab is a monoclonal antibody that specifically targets vascular endothelial growth factor (VEGF) receptor-2, blocking growth of new blood vessels in the tumor. Currently ramucirumab is approved only for advanced gastric cancer treatment. No other approved antiangiogenic drugs are available in the second-line setting for advanced NSCLC.

Approved second-line therapies for advanced NSCLC include docetaxel and erlotinib (Tarceva), and pemetrexed (Alimta) for nonsquamous NSCLC only. Clinical outcomes remain poor, however, with tumor shrinkage rates around 10% and median overall survival ranging between 7 and 9 months, Dr. Perol noted at the ASCO press briefing on targeted therapies. 

In the REVEL study, 1,253 patients with stage IV NSCLC that had progressed despite standard platinum-based therapy to receive docetaxel at 75 mg/m2 in combination with either ramucirumab at 10 mg/kg or placebo every three weeks on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or death.

Key Endpoints Met

The primary endpoint of overall survival was met, with ramucirumab reducing the risk of death by 14% (hazard ratio [HR] = 0.857; P = .0235), and prolonging median overall survival by 1.4 months, Dr. Pérol reported. Key secondary endpoints were also met, with ramucirumab reducing the risk of progression by 24% (HR = 0.762; P < .0001), prolonging progression-free survival by 1.5 months (from 3.0 to 4.5 months), and increasing response rates from 13.6% to 22.9% (P < .001).

The survival benefits were consistent in the major subgroups of patients, including squamous (26% of study patients) and nonsquamous subtypes, suggesting that this therapy could be suitable for all major subtypes of NSCLC.

Safety Profile

“The safety profile was quite good,” Dr. Pérol remarked, and no unexpected adverse events were identified. Grade ≥ 3 adverse events for patients receiving ramucirumab vs placebo included neutropenia (34.9% vs 28.0%), febrile neutropenia (15.9% vs 10.0%), fatigue (11.3% vs 8.1%), leukopenia (8.5% vs 7.6%), hypertension (5.4% vs 1.9%), and pneumonia (5.1% vs 5.8%).

Grade 5 adverse events were 5.4% in the ramucirumab group and 5.8% in the placebo group. Pulmonary hemorrhage (any grade) occurred in 2.1% of all patients receiving ramucirumab and 1.6% of all patients receiving placebo and 3.8% vs 2.4% among patients with squamous NSCLC.

“It is exciting to see progress in this disease, where the steps are small, but cumulative,” commented Gregory A. Masters, MD, ASCO expert on lung and head and neck cancers, and Director, Medical Oncology Fellowship, and Attending Physician, Helen F. Graham Cancer Center in Newark, Delaware. “We are excited to have another agent that shows activity, especially in this very difficult to treat second-line population of non–small cell lung cancer.”

This research was supported by ImClone, a wholly owned subsidiary of Eli Lilly. Dr. Pérol has a consultant or advisory role with Pfizer, Roche, Boehringer Ingelheim, Genentech, and Lilly; honoraria from Pfizer, Roche, Genentech, and Lilly, and other remuneration from Roche, Genentech, and Lilly; and is an advisory board member and/or consultant of the trial sponsor. For full disclosures of the study authors, view the study abstract at abstract.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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