“Stomach cancer has not had sufficient attention in terms of drug development, efforts in finding new drugs or really in understanding the fundamental biology until recently,” said Charles Fuchs, who leads Dana-Farber Cancer Institute’s Gastrointestinal Cancer Center. “I’ve been pleased to see over the past several years that more attention has been paid to the disease.”
That attention resulted in the Food and Drug Administration (FDA) approval of Cyramza (ramucirumab) on April 21 for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma (read the FDA announcement). Historically, gastric cancer treatment has been limited to chemotherapies developed for other cancers, Fuchs says. “That may seem like a subtle point, but most of the drugs used in gastric cancer were actually developed for other cancers and subsequently tested and approved for stomach cancer.”
Moreover, Cyramza is the first drug approved for patients whose gastric cancers have progressed on first-line treatment. While oncologists have been treating patients in the second-line treatment setting for years, until now, there has been no standard of care. That unmet need was a catalyst for the priority review the FDA granted last year to help speed along the potential approval (read more).
The approval was based on the phase 3 REGARD study, in which Fuchs was a lead investigator. The study found that patients who received Cyramza had a 1.4 month improvement in median overall survival over patients receiving best supportive care (5.2 months compared with 3.8 months), in addition to better progression-free survival. Side effects included high blood pressure and diarrhea, but overall, side effects were well managed and tolerable, he says.
Fuchs points out that the risk of certain side effects, such as fatigue and nausea, were actually lower in the Cyramza arm than in the placebo arm. “That may seem a bit odd, but patients with stomach cancer who have progressed on first-line therapy have symptoms from the disease,” he says. “What’s also interesting is that when you look at the results of the REGARD study, which I was involved in, and you compare those results to similarly designed studies where they compared second-line chemotherapy to placebo, the benefit is almost exactly the same (to Cyramza).”
He concludes that the benefit of Cyramza appears to be comparable to standard chemotherapy, but with a better side effect profile. The next step may be combining the drug with chemotherapy, which was the basis for the RAINBOW trial. This trial looked at the combination of Cyramza and paclitaxel. Results showed an even greater survival benefit not previously seen in second-line stomach cancer, Fuchs says.
“It wasn’t part of the approval because that study is more recent, but I hope the FDA, upon reviewing that study, will amend the approval to include the use of the drug with paclitaxel,” he says. “In my own practice, I anticipate it will be the principal way I use it to treat patients in that setting.”