Abstract
Addition of the MET inhibitor onartuzumab to erlotinib improves survival in MET-positive NSCLC.
Major finding: Addition of the MET inhibitor onartuzumab to erlotinib improves survival in MET-positive NSCLC.
Clinical relevance: This drug combination was associated with worse outcome in patients with MET-negative NSCLC.
Impact: Treatment with onartuzumab plus erlotinib warrants further study in MET-positive NSCLC.
Inhibitors of the EGF receptor (EGFR), such as erlotinib, prolong survival in patients with EGFR-mutant non–small-cell lung cancer (NSCLC), but acquired resistance limits the long-term clinical efficacy of these drugs. The tyrosine kinase receptor MET is frequently coactivated with EGFR in NSCLC and is associated with poor prognosis; in addition, MET amplification has been shown to contribute to erlotinib resistance in patients with EGFR-mutant NSCLC. Spigel and colleagues evaluated the activity and safety of erlotinib plus onartuzumab, a monovalent monoclonal anti-MET antibody that blocks its activation, in a randomized, placebo-controlled phase II trial of 137 patients with recurrent NSCLC. Patients received erlotinib in combination with either onartuzumab or placebo, and MET expression status in tumor tissue samples was assessed. Objective response rates did not differ among patient subgroups or treatment arms, and there was no change in progression-free survival (PFS) or overall survival (OS) with onartuzumab treatment in the intent-to-treat population. However, the addition of onartuzumab prolonged PFS (2.9 vs 1.5 months) and OS (12.6 vs 3.8 months) compared with placebo treatment among patients with MET-positive tumors; this beneficial effect was not affected by differences in baseline characteristics among patients. In contrast, combined MET and EGFR inhibition resulted in enhanced disease progression (PFS of 1.4 vs 2.7 months) and shorter survival (8.1 vs 15.3 months) in patients with MET-negative tumors compared with placebo plus erlotinib. Adverse events associated with onartuzumab treatment were generally grade 1 or 2 and included a higher incidence of peripheral edema and pneumonia compared with placebo treatment. These results suggest that dual inhibition of MET and EGFR may provide therapeutic benefit specifically to patients with MET-positive NSCLC and support ongoing phase III trials of this drug combination.
Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
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