Adding the mesenchymal-epithelial transition (MET) antibody onartuzumab to fluorouracil, leuecovorin, and oxaliplatin (mFOLFOX6) did not significantly improve clinical outcomes in patients with HER2-negative, MET-positive gastroesophageal adenocarcinoma, a study published in JAMA Oncology has shown.1
Because dysregulation of the MET signaling pathway is associated with poor prognosis in gastroesophageal adenocarcinoma, researchers sought to evaluate whether adding a MET inhibitor to standard chemotherapy would improve efficacy in patients with HER2-negative, MET-positive gastroesophageal cancer.
For the multicenter, double-blind study (Clinicaltrials.gov Identifier: NCT01662869), researchers enrolled 562 patients with adenocarcinoma of the stomach or gastroesophageal junction with metastatic disease not amenable for curative therapy. Of those, 38.5% and 37.6% were considered MET 2+ and MET 3+, defined as at least 50% of tumor cells showing moderate or strong staining intensity, respectively.
Participants were randomly assigned 1:1 to receive mFOLFOX6 plus onartuzumab 10 mg/kg intravenously or mFOFLOX6 plus placebo.
After enrollment was stopped early, results showed there was no significant difference in overall survival (hazard ratio [HR], 0.82; 95% CI, 0.59-1.15; P = .24), progression-free survival (HR, 0.90; 95% CI, 0.71-1.16; P = .43), or overall response rate (46.1% vs 40.6%) between the 2 treatment arms in the overall population.
Similarly among the MET 2+/3+ population, the addition of onartuzumab to mFOLFOX6 did not significantly improve overall survival (HR, 0.64; 95% CI, 0.40-1.03; P = .06), progression-free survival (HR, 0.79; 95% CI, 0.54-1.15; P = .22), or overall response rate (53.8% vs 44.6%).
The safety profile of onartuzumab was consistent with previously reported safety data.
1. Shah MA, Bang Y-J, Lordick F, et al. Effect of fluorouracil, leucovorin, and oxaliplatin with or without onartuzumab in HER2-negative, MET-positive gastroesophageal adenocarcinoma: the METGastric tandomized clinical trial. JAMA Oncol. 2016 Dec 1. doi: 10.1001/jamaoncol.2016.5580. [Epub ahead of print]