Combination Therapy Fails in Late-Stage Clinical Trial of Advanced Gastric Cancer

Eli Lilly and Company recently announced results from the phase 3 RAINFALL clinical trial, which evaluated a combination of ramucirumab (Cyramza) plus cisplatin and capecitabine in patients with gastric cancer, according to a press release.

While the clinical trial met its primary endpoint of progression-free survival (PFS), the combination did not improve overall survival in 645 patients with HER2-negative metastatic gastric or gastroesophageal junction adenocarcinoma, which was a secondary endpoint of the trial, according to Lilly.

Based on these results, Lilly will not pursue regulatory approval for ramucirumab plus cisplatin and capecitabine. However, this does not impact the current indications for ramucirumab, including gastric cancer, according to the release.

"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, MD, PhD, 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 safety profile of ramucirumab was consistent with previous trials, with patients experiencing hypertension, hand-foot syndrome, and fatigue in the RAINFALL study.

Currently, ramucirumab is a standard of care for patients with advanced gastric cancer prior to receiving chemotherapy, according to Lilly.

Thus far, there have been 6 positive phase 3 clinical trials of ramucirumab, which demonstrated benefit in advanced forms of gastric, non-small cell lung (NSCLC), and colorectal cancer, according to the release.

An ongoing phase 3 study in advanced urothelial carcinoma also met its primary endpoint of PFS, while 2 other studies in hepatocellular carcinoma and EGFR-positive NSCLC are ongoing.

“Lilly is deeply committed to patients with this aggressive disease, and Cyramza remains a standard of care in the second-line treatment paradigm for advanced gastric cancer patients around the world,” Dr Garraway said. “We thank the patients, their caregivers and investigators for their support of and participation in the RAINFALL study."