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Ramucirumab increased survival among patients with advanced gastric cancer
The novel drug ramucirumab significantly improved survival compared with placebo among patients with metastatic refractory gastric or gastroesophageal junction cancer, according to results of the phase 3 REGARD study presented at the Gastrointestinal Cancers Symposium.
VEGF and VEGF-receptor 2 mediated signaling, as well as angiogenesis, may contribute to the development of gastric cancer. Ramucirumab (IMC-1121B, ImClone Systems) is a human monoclonal antibody that targets VEGF-receptor 2.
Charles S. Fuchs, MD, MPH, professor in the department of medicine at Harvard Medical School, and colleagues conducted a placebo-controlled, double-blind, international trial to evaluate the safety and efficacy of ramucirumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma that progressed on first-line platinum and/or fluoropyrimidine therapy.
Researchers randomly assigned 355 patients to receive ramucirumab (n=238) or placebo (n=117) every 2 weeks until disease progression, unacceptable toxicity or death. All patients also received best supportive care.
Eligible patients had disease progression within 4 months after first-line therapy or within 6 months after adjuvant therapy.
OS served as the primary endpoint. Secondary endpoints included PFS, 12-week PFS, overall response rate and safety.
Patients assigned to ramucirumab experienced significantly longer median OS (5.2 months vs. 3.8 months; HR=0.776; 95% CI, 0.603-0.998) and PFS (2.1 months vs. 1.3 months; HR=0.483; 95% CI, 0.376-0.620) than patients assigned to placebo.
Patients in the ramucirumab group also had a higher rate of 12-week PFS rate (40% vs. 16%), a higher overall response rate (3.4% vs. 2.6%) and higher disease control rate (49% vs. 23%) compared with those in the placebo arm (P<.0001).
The most frequent grade 3 or higher adverse events reported by patients assigned to ramucirumab were hypertension, anemia, abdominal pain, ascites, fatigue, decreased appetite and hyponatremia.
For more information:
Fuchs CS. Abstract #LBA5. Presented at: Gastrointestinal Cancers Symposium; Jan. 24-26, 2013; San Francisco.
Disclosure: The researchers report serving as consultants/advisers for, as well as receiving research funding and honoraria from, Amgen, Bayer, Bristol-Myers Squibb, Genentech, Infinity Pharmaceuticals, ImClone Systems, Lilly, Merck KGaA, Novartis, Pfizer, Roche and other pharmaceutical companies.
Perspective
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The positive REGARD study likely will establish a new standard of care for patients with refractory gastric and gastro-esophageal cancer. Ramucirumab is a fully human IgG1 monoclonal antibody targeting VEGF receptor-2, and it has been shown to modestly improve both OS and PFS in this patient population. The findings of this study will rekindle the interest in further developing inhibitors of the VEGF pathway, following initial disappointment with the results of the first-line study with bevacizumab (Avastin, Genentech). However, a predictive biomarker is desperately needed to help select patients who are more likely to respond to ramucirumab given its modest improvement in outcome, cost and toxicities.