In the REGARD phase III trial, adding Eli Lilly's ramucirumab to best supportive care for late-stage gastric or gastroesophageal cancer boosted overall survival to 5.8 months compared with 3.8 months among patients given placebo.
Far more common in Asia than it is in the West, gastric cancer remains a leading cause of cancer death worldwide, with a dearth of treatment options for advanced disease. In the REGARD phase III trial, however, the addition of Eli Lilly's monoclonal antibody ramucirumab to best supportive care for late-stage gastric or gastroesophageal cancer increased overall survival to 5.8 months, compared with 3.8 months in patients given best supportive care and placebo.
Based on these results, announced in January at the American Society of Clinical Oncology 2013 Gastrointestinal Cancers Symposium in San Francisco, CA, Lilly plans to submit the VEGF receptor–2 inhibitor for regulatory approval in the United States and in Europe this year.
Given the limited overall survival benefits and meager improvements in progression-free survival shown in the REGARD trial—2.1 months compared with 1.3 months with placebo—some experts speculate that regulators might wait for the results of the ongoing RAINBOW phase III study, which combines ramucirumab with paclitaxel.
However, Hope Uronis, MD, an assistant professor at the Duke Cancer Institute in Durham, NC, who was not involved in the trial, says the REGARD results are a step in the right direction. “They add to the treatment arsenal for a disease in which the therapeutic landscape is bleak,” she says.
If it is approved, ramucirumab would be the second targeted treatment for gastric cancer on the market after trastuzumab (Herceptin; Genentech), which is given with chemotherapy to patients with HER2-positive tumors and limited to first-line treatment. The REGARD trial results come on the heels of a recent disappointment in the REAL3 trial, in which the EGF receptor inhibitor panitumumab (Vectibix; Amgen) failed to improve overall survival in advanced gastric cancer.
Researchers are looking forward to new possibilities with MET inhibitors, which Uronis describes as “the next big thing in gastric cancer.” Several compounds are in clinical development, among them Genentech's monoclonal antibody onartuzumab, which recently began a phase III trial in combination with chemotherapy in patients with HER2-negative and MET-positive gastroesophageal cancer.
However, the ramucirumab findings offer 2 positive notes, according to Uronis. “It's impressive that the drug produced overall survival benefits as a second-line treatment, where existing drugs generally perform very poorly,” she says. “There were also quality of life improvements, which is something we're always looking for.”