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Onartuzumab plus erlotinib prolonged survival in MET-positive NSCLC
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The addition of onartuzumab to erlotinib significantly improved PFS and OS in patients with advanced, MET-positive non–small cell lung cancer, according to results of a phase 2 trial.
However, MET-negative patients treated with the combination demonstrated worse outcomes.
The analysis included 137 patients with recurrent NSCLC.
Researchers assigned 69 patients to treatment with 150 mg daily erlotinib (Tarceva; Genentech, Astellas Pharma) plus IV onartuzumab (MetMAb, Genentech), a humanized monoclonal antibody and MET antagonist. The other 68 patients received erlotinib plus placebo.
Researchers assessed MET expression — associated with worse prognosis in NSCLC — in 128 patients. Of them, 66 (52%) were MET positive.
Median follow-up was 10.4 months (range, .1-18.4).
Overall, the rates of median PFS (2.6 months for placebo vs. 2.2 months for onartuzumab; HR=1.09; P=.69) and OS (7.4 months for placebo vs. 8.9 months for onartuzumab; HR=.80; P=.34) did not differ significantly between groups.
However, researchers did observe significant variation based on patients’ MET status.
MET-positive patients who received onartuzumab experienced lower risk for disease progression (HR=0.53; P=.04) and significantly longer OS 12.6 months vs. 3.8 months; HR=0.37; P=.002) than patients assigned to placebo.
MET-negative patients who received onartuzumab experienced earlier disease progression (1.4 months vs. 2.7 months; HR=1.82; P=.05) and shorter OS (8.1 months vs. 15.3 months; HR=1.78; P=.16) than those assigned to placebo.
The rate of discontinuation due to adverse events was higher in the onartuzumab arm than the placebo arm (11.6% vs. 4.4%); it also was higher among MET-positive patients than MET-negative patients (22.9% vs. 6.5%). The most common adverse events in both arms were rash, diarrhea, fatigue and nausea.
“These results highlight the importance of diagnostic development in clinical oncology studies,” the researchers wrote. “The activity observed in this study, combined with the prevalence of MET and its association with poor prognosis in other indications, provides a rationale for further clinical evaluation of NSCLC and other indications.”
A randomized phase 3 study designed to evaluate erlotinib with or without onartuzumab in patients with MET-positive NSCLC is underway, researchers said.
Disclosure: The researchers report employment or leadership positions with, research funding and honoraria from, consultant or advisory roles with, and stock ownership in Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Merck, Pfizer, Roche and other pharmaceutical companies.
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