Addition of MET Inhibitor to First-Line Chemotherapy in Advanced Gastric Cancer


Key Points

  • In patients with MET-positive gastric or gastroesophageal adenocarcinoma, study treatment with the MET inhibitor rilotumumab and chemotherapy was stopped early due to excessive mortality in the rilotumumab group.
  • Overall survival was significantly poorer in the rilotumumab group. 

The phase III RILOMET-1 trial showed no survival benefit of adding the MET inhibitor rilotumumab to first-line epirubicin, cisplatin, and capecitabine in patients with advanced MET-positive gastric or gastroesophageal junction adenocarcinoma. These results were reported in The Lancet Oncology by Catenacci et al.

Study Details

In the double-blind trial, 609 patients from 152 sites in 27 countries were randomized between November 2012 and November 2014 to receive rilotumumab at 15 mg/kg (n = 304) or placebo (n = 305) plus open-label chemotherapy with epirubicin at 50 mg/m2, cisplatin at 60 mg/m2, and capecitabine at 625 mg/m2 twice daily in 21-day cycles for up to 10 cycles. After completion of chemotherapy, patients continued to receive rilotumumab or placebo until disease progression or intolerability. Randomization was stratified by disease extent and performance status.The primary endpoint was overall survival in the intent-to-treat population.

Treatment Stopped Early

Study treatment was stopped early after a higher number of deaths in the rilotumumab group was found by an independent data monitoring committee. Median follow-up was 7.7 months in the rilotumumab group and 9.4 months in the placebo group. Median overall survival was 8.8 months vs 10.7 months (stratified hazard ratio = 1.34, P = .003).

Adverse Events

The most common grade ≥ 3 adverse events in the rilotumumab vs placebo groups were neutropenia (29% vs 32%), anemia (12% vs 14%), and fatigue (10% vs 12%). Serious adverse events occurred in 48% vs 50%. Death due to adverse events occurred in 14% vs 10%. Fatal adverse events due to disease progression occurred in 11% vs 8%, and fatal adverse events not due to disease progression occurred in 3% vs 3%.

The investigators concluded: “Ligand-blocking inhibition of the MET pathway with rilotumumab is not effective in improving clinical outcomes in patients with MET-positive gastric or gastro-oesophageal adenocarcinoma.”

The study was funded by Amgen.

David Cunningham, MD, of The Royal Marsden Hospital, London, is the corresponding author of The Lancet Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.