Could blocking MET triple survival?

This study examined the effectiveness of onartuzumab (MetMAb) and erlotinib (Tarceva) as treatment for non-small cell lung cancer patients.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. In many patients, a mutation in the EGFR gene, which is involved in normal cell growth, causes uncontrolled cancer growth and spread. Several drugs, such as erlotinib (Tarceva), inhibit the stimulating effect EGFR has on cellular growth. Erlotinib has been shown to improve both overall survival and progression free survival (the time it takes for the cancer to progress despite treatment) in EGFR-positive NSCLC patients. However, eventually patients may become resistant to erlotinib and cancer may progress despite treatment.

A second genetic mutation, one in the MET gene, is also found in many NSCLC patients and is associated with worse prognosis. MET and EGFR mutations are often found together in NSCLC patients, and MET mutations have been found to increase the risk of developing resistance to erlotinib. Onartuzumab (MetMAb) is a new drug developed for the treatment of MET-positive cancers. The current study examines the effectiveness and safety of a combination treatment using onartuzumab and erlotinib in the care of NSCLC patients.

137 patients diagnosed with advanced NSCLC were included in this study. 52% of patients were found to be MET-positive. Patients were randomly assigned to receive either a combination of onartuzumab and erlotinib (69 patients), or a combination of erlotinib and a placebo (68 patients). Patients received erlotinib once per day by oral pills, while onartuzumab, or the placebo, were administered intravenously once every 3 weeks.

Among MET-positive patients, onartuzumab treatment led to a 47% reduction in the risk for disease progression despite treatment. Overall survival was nearly tripled among patients receiving onartuzumab, from 3.8 months for patients receiving a placebo to 12.6 months.

In patients without MET mutations however, onartuzumab led to earlier disease progression and shorter survival times. Common adverse effects seen in all treatment groups included rashes, diarrhea, and fatigue.

This study concluded that onartuzumab, in combination with erlotinib, is an effective treatment for MET-positive NSCLC patients.

This small, early phase trial was funded by Genetech, the manufacturer of both MetMAb and Tarceva. A larger phase III trial is awaited to confirm these results.