Abstract
Based on data from the key phase III REGARD trial, the FDA approved ramucirumab as second-line therapy for patients with advanced stomach cancer and gastroesophageal junction adenocarcinoma.
On April 21, the FDA gave physicians the go-ahead to use ramucirumab (Cyramza; Lilly Oncology) as second-line therapy for patients with advanced stomach cancer or gastroesophageal junction (GEJ) adenocarcinoma. Ramucirumab is the first drug approved in this setting.
“The frequency of gastroesophageal junction adenocarcinoma is rising faster than any other cancer in the U.S., making this a public health issue,” says Charles Fuchs, MD, MPH, director of Dana-Farber Cancer Institute's Gastrointestinal Cancer Center in Boston, MA. Fuchs helped develop ramucirumab and led REGARD, a phase III trial with results, first reported in 2013, that were key to ramucirumab receiving FDA approval for single-agent use (Lancet 2014;383:31–9).
Ramucirumab is a fully humanized monoclonal antibody that binds to VEGFR-2, a main driver of angiogenesis in tumors, and acts as an antagonist by blocking the VEGFR-2 ligands VEGF-A, VEGF-C, and VEGF-D.
In the REGARD study, two thirds of the 355 participants with inoperable or metastatic advanced stomach cancer or GEJ adenocarcinoma received ramucirumab, and the rest placebo. All had previously received fluoropyrimidine-based or platinum-based chemotherapy. Ramucirumab extended median overall survival (OS) by 1.4 months, and median progression-free survival (PFS) by 0.8 months.
Although these improvements may seem modest, Fuchs points out that the benefit of a new drug in medical oncology is often incremental. He also notes that ramucirumab “offers a superior toxicity profile” compared to standard cytotoxic drugs, with patients tolerating its main side effect, hypertension, very well.
Earlier this year, Lilly Oncology reported results from a second phase III study, RAINBOW, in which 665 patients with metastatic stomach cancer received either ramucirumab plus paclitaxel, or paclitaxel alone. Combination therapy extended median OS by 2.2 months and median PFS by 1.5 months, with patients reporting manageable side effects and improved quality of life.
A fully humanized monoclonal antibody, ramucirumab binds to VEGFR-2 (above), a main driver of angiogenesis in tumors. It blocks the VEGFR-2 ligands VEGF-A, VEGF-C, and VEGF-D.
A fully humanized monoclonal antibody, ramucirumab binds to VEGFR-2 (above), a main driver of angiogenesis in tumors. It blocks the VEGFR-2 ligands VEGF-A, VEGF-C, and VEGF-D.
Taking data from both trials into account, Fuchs believes “this really sets the mark, namely that ramucirumab-based regimens should be the standard of care for second-line therapy.” He now wants to see ramucirumab tested against standard first-line chemotherapy for stomach cancer, but acknowledges that determining this standard may be challenging, as there is “not necessarily a clear winner” among currently available treatments.
“I don't know that drugs targeting VEGF receptors are superior to those that go after VEGF ligands,” adds Fuchs, “but I don't think there's any question that VEGF inhibition has activity in gastric cancer.”
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