MetMAb/erlotinib improved PFS, OS in patients with NSCLC

ESMO 35th Congress

MILAN — MetMAb and erlotinib in patients with MET expression in non-small-cell lung cancer improved both PFS and OS with no unexpected adverse events. Researchers therefore recommend a prospective study to compare the two therapies in patients selected for MET-positive tumors.

David Robert Spigel, MD, program director of Lung Cancer Research at the Sarah Cannon Research Institute, Nashville, Tenn., presented the results of the double-blind, phase 2 study here.

The study included 128 patients with advanced non-small cell lung cancer randomly assigned to either erlotinib plus placebo (n=64) or erlotinib plus MetMAb (n=64) — a monoclonal antibody that binds to the MET receptor.

Spigel and colleagues tested for mutations in the EGFR gene and expression of MET in pooled tumor samples.

In 51% of patients with MET tumor expression, patients assigned MetMAb and erlotinib had better OS (HR=0.55; 95% CI, 0.25-1.16; P=.11) and longer PFS (HR=0.56; 95% CI, 0.31-1.02; P=.05) when compared with erlotinib plus placebo.

However, in patients without MET expression, PFS (HR=2.01; 95% CI, 1.04-3.91; P=.04) and OS (HR=3.26; 95% CI, 1.20-8.80; P=.01) appeared to do worse with MetMAb and erlotinib, which may be due to MetMAb interfering with erlotinib activity in these patients, according to Spigel.

Spigel concluded that the findings of this trial “need to be validated in a larger randomized phase 3 trial in patients selected for MET expression.”

The results of this trial are important for three reasons. First, this is the second trial in lung cancer where targeting of MET in combination with erlotinib suggests a better outcome. “This confirms that MET is a relevant target in cancer. Also, the present Genentech-sponsored trial has identified a putative biomarker, namely MET immunohistochemical positivity, which appears to be easy to implement as immunohistochemistry testing is daily practice in pathology labs. Finally, in the present trial the biomarker-positive population not only derived a benefit in PFS, but also an almost statistical OS benefit, which is remarkable taking into account the small number of patients. One note of caution, however, is that these phase 2 results should be validated in a larger phase 3 trial.

–Jean-Charles Soria, MD

Professor, Institute Gustave Roussy, Paris, France

For more information:

Spigel D. #LBA15. Presented at: the ESMO 35th Congress; Oct. 8-12, 2010; Milan, Italy.

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