Mixed results in gastric cancer RAINBOW trial

Eli Lilly and Company announced top-line results from its Phase III RAINFALL study of Cyramza (ramucirumab) in combination with cisplatin and capecitabine or 5-FU (5-fluorouracil) in the first-line treatment of patients with HER2-negative metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The trial met its primary endpoint of progression-free survival (PFS) but did not improve overall survival (OS), a secondary endpoint. The results will be submitted for presentation at a future medical meeting. The safety profile observed in the RAINFALL study was consistent with what has been previously observed for ramucirumab. Grade greater than 3 adverse events occurring at a rate of five percent or greater and that were higher on the ramucirumab-plus-cisplatin-and-capecitabine/5-FU arm compared to the placebo-plus-cisplatin-and-capecitabine/5-FU arm were hypertension, hand-foot syndrome, and fatigue.

"While we hoped that the positive PFS outcome would have translated into an OS benefit, these RAINFALL results highlight the challenges associated with improving outcomes for people with advanced gastric cancer," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "This is underscored by the fact that there have been no major advances over standard chemotherapy in the first-line HER2-negative gastric cancer treatment setting in the last decade." The company does not intend to seek regulatory approval based on the results of the RAINFALL study. The outcome of RAINFALL does not have any impact on current ramucirumab approvals.

After becoming the first FDA-approved agent to treat advanced gastric cancer after prior chemotherapy in 2014 based on two pivotal Phase III studies, ramucirumab is now a standard of care in this setting around the world. This is supported by global and local treatment guidelines, including NCCN, JGCA and ESMO. Overall, there have been six positive Phase III trials of ramucirumab to date. Previously completed Phase III studies of ramucirumab have demonstrated benefit in advanced forms of gastric, non-small cell lung and colorectal cancer - three of the world's leading causes of cancer-related death. An ongoing Phase III trial in advanced urothelial carcinoma has also met its primary endpoint of PFS; those initial data were presented at the ESMO 2017 Congress and OS data are expected in mid-2018. Two other ongoing Phase III studies of ramucirumab - in hepatocellular carcinoma and EGFR-positive non-small cell lung cancer - are ongoing, with expected data readouts in 2018.