Benefit of Rilotumumab + Chemo in Gastric Cancer Tied to High MET Expression
(CHICAGO, IL)—High MET expression may predict clinical benefit in patients with locally advanced or metastatic gastric or esophagogastric function cancer treated with rilotumumab plus epirubicin, cisplatin, and capecitabine as well as poor prognosis for those treated with epirubicin, cisplatin, and capecitabine alone, according to results of a study presented at the 2012 American Society of Clinical Oncology Annual Meeting.
High tumor MET levels are known to be associated with poor prognosis in gastric cancer, noted study author Kelly S. Oliner, MD, of Amgen Inc., Thousand Oaks, CA, and colleagues.
This double-blind, placebo-controlled phase 2 study explored MET pathway biomarkers to identify patients who may benefit from rilotumumab (AMG 102), an investigational, fully human, monoclonal antibody to HGF/SF, the ligand of the MET receptor. Investigators used archival tumor samples from a phase 2 study that randomized 121 patients with gastric or esophagogastric function cancer to 15mg rilotumumab + epirubicin, cisplatin, and capecitabine (Arm A, n=40), 7.5mg/kg rilotumumab + epirubicin, cisplatin, and capecitabine (Arm B, n=42), or placebo plus rilotumumab + epirubicin, cisplatin, and capecitabine (Arm C, n=39).
Tumor samples were evaluable for MET protein from 62 patients in Arms A + B and 28 in Arm C. Those with METHigh tumors (>50% tumor cells positive) in Arms A + B had improved median overall survival (OS; 11.1 months) vs patients in Arm C (5.7 months; HR=0.29; P=0.012).
Patients with METLow tumors (≤50% positive) in Arms A + B had a trend toward unfavorable OS compared with those in Arm C (HR=1.84). In Arm C, in which patients received chemotherapy only, those with METHigh tumors had poorer OS (HR=3.22) than those with METLow tumors. Dr. Oliner observed similar trends for progression-free survival.
“High tumor MET expression can predict clinical benefit for the addition of rilotumumab to ECX in patients with advanced gastric or esophagogastric cancer. Also, predefined dichotomization schemes for tumor MET gene copy number and baseline plasma levels of total HGF or sMET did not correlate with OS or PFS,” Dr. Oliner concluded.