FDA Approves Drug Combo for Gastric/GEJ Adenocarcinoma

The US Food and Drug Administration (FDA) approved the monoclonal anti-VEGFR2 antibody ramucirumab (Cyramza) in combination with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. This follows an approval in April of this year for these malignancies that were refractory to or progressive following first-line treatment with platinum-based or fluoropyrimidine chemotherapy.

The new approval, which came out of an orphan drug designation by the FDA, is based on a large study of 655 patients with previously-treated advanced or metastatic gastric or GEJ adenocarcinoma. Patients received either the combination of ramucirumab and paclitaxel (330 patients) or placebo with paclitaxel (335 patients). The median overall survival was 9.6 months with ramucirumab and 7.4 months with placebo, yielding a hazard ratio (HR) of 0.81 (95% CI, 0.68-0.96; P = .017).

Progression-free survival was also significantly improved with ramucirumab. The HR for progression-free survival was 0.64 (95% CI, 0.54-0.75; P < .001).

Among 656 patients who received at least one dose of the study drug, the most frequent adverse events were fatigue/asthenia, neutropenia, diarrhea, and epistaxis. The most common serious adverse events with ramucirumab were neutropenia (3.7% of patients) and febrile neutropenia (2.4% of patients).

These results were initially presented at the 2014 American Society of Clinical Oncology Gastrointestinal Cancers Symposium in January. At the time, the lead author Hansjochen Wilke, MD, of the Kliniken Essen-Mitte in Germany said the 2-month improvement in overall survival was “an astonishingly good result in such a challenging patient population. The result was statistically significant and also clinically meaningful.”

Ramucirumab hasn’t been completely successful in treating these malignancies, however. The combination drug seems to make an important difference, as results presented at the 2014 ASCO Annual Meeting showed: adding ramucirumab to the FOLFOX regimen did not delay progression among patients with untreated advanced gastric or esophageal adenocarcinoma. The drug did provide a longer progression-free survival and improved disease control rate in certain patients, however.

Ramucirumab, an angiogenesis inhibitor, in combination with other agents such as docetaxel has also shown promise in other malignancies including non–small-cell lung cancer. It is currently under investigation in other cancers including advanced liver cancer and other solid tumors.