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Greater MET/CEP7 expression may predict therapy response in NSCLC
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Patients with non–small cell lung cancer who had higher MET positivity appeared less likely to harbor other cancer drivers, according to research presented at the World Conference on Lung Cancer.
Thus, a greater MET-to-CEP7 ratio — or a comparison of the MET copy number to the number of chromosome 7 centromeres — may predict benefit from treatment with crizotinib (Xalkori, Pfizer) in patients with NSCLC, according to the researchers.
“Generally, there are two ways that the number of copies of the MET gene can be increased: the tumor can make multiple copies of the entire chromosome on which it sits — chromosome 7 — or it can amplify just the MET region,” Sinead A. Noonan, MD, senior thoracic oncology fellow at University of Colorado School of Medicine, said in a press release. “In the first case, MET is unlikely to be the specific driver of the cancer’s biology. But if the MET region is amplified separate from the rest of the chromosome, this should suggest that the MET gene is indeed the area of specific importance to the cancer.”
Researchers defined MET copy number expression as low (≥ 5 to ˂ 6), intermediate (≥ 6 to ˂ 7) and high (≥ 7) and MET/CEP7 ratio as low (≥ 1.8 to ≤ 2.2), intermediate (˃ 2.2 to ˂ 5) and high (≥ 5).
The analysis included data from 1,164 patients with NSCLC (median age, 61 years; 60% women).
The researchers evaluated MET copy number in 700 patients, of whom 16% (n = 113) had a mean MET/cell of at least 5.
Researchers then compared MET copy number to the number of CEP7 to evaluate how specifically MET was amplified compared with the chromosome as a whole. Fifty-two patients (4.5%) had MET/CEP7 expression greater than or equal to 1.8. Of those patients, 98% (n = 50) had one or more other oncologic driver tested.
Among patients with at least one additional driver oncogene, the expression of alternate drivers varied based on MET copy number vs. MET/CEP7 ratio for low (67% vs. 55%), intermediate (70% vs. 50%) and high (43% vs. 0%) cutoffs. Thus, patients with high MET/CEP7 expression — more likely to be men (4% vs. 1.6%; P = .019) — harbored no other drivers.
In a proof-of-concept analysis of three patients — all of whom had high MET/cell — the patient who also had high MET/CEP7 was the only patient who achieved a complete response to first-line crizotinib.
“There’s definitely a population of patients with cancers sensitive to MET inhibition that can be identified by MET copy number increase,” Noonan said. “The challenge is finding these people accurately so they can get the best, most personalized approach to treatment possible.” – by Cameron Kelsall
Reference:
Noonan SA, et al. Defining MET Copy Number Driven Lung Adenocarcinoma Molecularly and Clinically. Presented at: 16th World Conference on Lung Cancer; Sept. 6-9, 2015; Denver, Colorado.
Disclosure: The researchers report no relevant financial disclosures.