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Ramucirumab Prolongs Survival in Advanced Gastric Cancer

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Key Points

  • There is currently no approved treatment for advanced gastric cancer that has progressed after first-line therapy, but ramucirumab, a monoclonal antibody VEGFR-2 antagonist, has shown promising results with modest side effects.
  • In a phase III trial, patients treated with ramucirumab had a median overall survival of 5.2 months vs 3.8 months in the placebo group.
  • Twelve-week progression-free survival was 40% in the ramucirumab group vs 16% for the placebo group.

An investigational targeted drug that reduces blood flow to tumors prolonged the survival of patients with advanced stomach cancer after standard treatments failed, according to results of large multicenter clinical trial reported by Charles S. Fuchs, MD, MPH, of Dana-Farber Cancer Institute, and colleagues in The Lancet. Patients receiving the monoclonal antibody ramucirumab also experienced a longer delay before the cancer progressed than those who were given a placebo in the randomized, controlled phase III trial, the investigators reported.

Because of the antibody’s selective action, patients receiving ramucirumab generally had modest side effects, though they had slightly increased rates of high blood pressure compared to the control patients.

“It’s really impressive that an antibody [with very few] side effects could provide a survival benefit,” said Dr. Fuchs, Director of Dana-Farber’s Center for Gastrointestinal Cancer.

Promising Targeted Treatment for Gastric Cancer

Advanced stomach cancer is typically treated with chemotherapy, but there is currently no approved second-line treatment if the cancer continues to progress.

“We realized that we need better treatments for stomach cancer because, for the most part, the current paradigm for using routine chemotherapy just isn’t enough,” said Dr. Fuchs. “We need to develop targeted agents for this disease that really focus on our understanding of the biology.”

Unlike standard toxic chemotherapeutic agents that kill cancer cells or prevent them from dividing, ramucirumab targets protein signals in the circulation that trigger the formation of new blood vessels to support tumors’ growth and spread. Ramucirumab is designed to block signaling through the VEGF Receptor-2 (VEGFR-2), reducing angiogenesis and starving the tumors of nutrients. Blocking VEGFR-2 in animal models slowed the growth of stomach cancer in mice.

REGARD Trial

The REGARD trial involved 355 patients with advanced gastric or gastroesophageal junction cancer who were treated at 119 medical centers in 29 countries. Patients were randomly assigned to receive ramucirumab every 2 weeks plus best supportive care (n = 355) or placebo plus best supportive care (n = 117).

The study ended in July 2012. Median overall survival was 5.2 months in the ramucirumab group vs 3.8 months in the placebo group (P = .047). The estimated survival at 6 months was 41.8% in patients receiving ramucirumab and 31.6% in the patients who received placebo.

The drug delayed progression of the cancer by 52%. Patients treated with ramucirumab had a 12-week progression-free survival of 40% compared to 16% for the placebo group; the researchers reported that the disease was under control for a median of 4.2 months with ramucirumab and for 2.9 months in the placebo group.

“What we found is that the patients who received the antibody had a significant improvement in their survival as well as a reduced rate of cancer progression,” Dr. Fuchs said. “The results were encouraging, and we hope that the drug will ultimately be approved for routine use for patients with stomach cancer.” He added that clinical trials are underway to find out if adding ramucirumab to chemotherapy “can get even better results.”

Adverse effects were common in both groups, and the incidence of serious side effects was comparable. However, hypertension occurred in 7.6% of patients on ramucirumab compared with 2.6% on placebo. The drug did not appear to cause effects sometimes seen with antiangiogenic drugs such as increased bleeding blood clots, and perforations of the stomach and intestines, according to the report.

The research was funded by Eli Lilly and Company and ImClone Systems.

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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