Federico Cappuzzo, MD, Director of the Medical Oncology Department at Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy, pointed out that the abstracts presented by Spigel et al and Camidge et al at the ASCO Annual Meeting explored the same target but with different results. The first evaluated the role of the anti-MET agent onartuzumab combined with erlotinib (Tarceva) in MET-positive non–small cell lung cancer (NSCLC), and the second evaluated the effects of crizotinib (Xalkori) in MET-amplified NSCLC.

Dr. Cappuzzo described previous data showing that patients with squamous NSCLC with intermediate or high levels of MET expression were all current or former smokers. “This is an important message. If we are looking for patients with MET amplification, we should probably look at smoking history and not only at histology,” he stated.

MET Testing Issues

Previous studies have shown that not all MET-positive patients on immunohistochemistry (IHC) are always MET-amplified on fluorescence in situ hybridization (FISH) and suggest that anti-MET agents would be effective in only 3% to 4% of patients.

“Perhaps that is why the study presented by Dr. Spigel was negative. We saw detrimental effects, especially where we expected the drug to work—that is, in epidermal growth factor receptor (EGFR)-mutated NSCLC,” he said.

Dr. Cappuzzo said it is possible that the negative findings were related to the difficulties in testing for MET. The study included patients evaluated only with IHC, but a consistent proportion of patients who test positive for MET expression on IHC do not have MET-amplified disease, he said. “An IHC +3 score needs to be confirmed by FISH,” he stated.

“MET remains an important target, but only in 3% to 4% of cases of NSCLC with gene amplification. We need to define the best methods and cutoff for MET amplification. We know this is detectable in smokers irrespective of histology,” he said.

“IHC or MET gene copy number are not optimal for detecting patients potentially sensitive to anti-MET strategies,” Dr. Cappuzzo continued. “Finally, new studies with anti-MET agents should be conducted only in properly selected patients,” he emphasized. ■

Disclosure: Dr. Cappuzzo reported no potential conflicts of interset.