Abstract
A phase II trial of the MET inhibitor capmatinib found that 72% of treatment-naïve patients responded to the drug, whereas the response rate for previously treated patients was 39.1%. The drug's side effects include peripheral edema, nausea, and vomiting.
Capmatinib (Novartis) can shrink tumors in up to 72% of patients with non–small cell lung cancer (NSCLC) who have MET mutations, according to trial results presented at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany, in October. The results also suggest that the drug targets brain metastases that can develop in these patients.
About 3% to 4% of patients with NSCLC have MET alterations, most of which are exon 14–skipping mutations. No drugs have been approved for patients who have these mutations, but on the strength of a phase I study, the FDA earlier this year granted breakthrough designation to Pfizer's crizotinib (Xalkori) as a second-line treatment. Several other MET inhibitors are in clinical trials.
The phase II GEOMETRY mono-1 trial is testing capmatinib in patients with advanced NSCLC harboring MET exon 14–skipping mutations. At the ESMO Congress, researchers reported preliminary results for 94 patients who had at least 18 weeks of follow-up; 25 were newly diagnosed with the disease and 69 had already received one or two therapies. The overall response rate (ORR) among treatment-naïve patients was 72%, versus 39.1% in those who had received previous treatment. Capmatinib penetrates the blood–brain barrier, and the researchers found that it shrank brain metastases in some patients.
The most common side effect of the drug was peripheral edema, a frequent adverse effect of MET inhibitors that occurred in 49% of trial participants. About 43% of patients had nausea and 28.5% reported vomiting. “I'm impressed with the data,” says Ravi Salgia, MD, PhD, of City of Hope in Duarte, CA, who wasn't connected to the research, noting that the ORR is high and that the drug appears to be relatively well tolerated.
Before the study, “it was questionable if mutation of MET exon 14 was really a driver” of NSCLC, says co-author Juergen Wolf, MD, of University Hospital of Cologne in Germany. The high response rate suggests that it is and that patients “can be treated effectively with a MET inhibitor,” he says.
Data on duration of response are not yet mature—median follow-up was for 5.6 months—and the researchers plan to continue tracking patients to determine how long the responses last and to evaluate progression-free survival, adds co-author Rebecca Suk Heist, MD, of Massachusetts General Hospital in Boston.
Although the verdict on the different MET inhibitors isn't in, capmatinib's strong response among treatment-naïve patients and effects on brain metastases suggest “it's at the head of the pack,” says Balazs Halmos, MD, of Montefiore Medical Center in New York, NY.
However, testing for MET mutations in newly diagnosed patients is not yet standard practice, notes Mark Awad, MD, PhD, of Dana-Farber Cancer Institute in Boston. Because the drug produces responses in treatment-naïve patients, the study “highlights the need for broad-based testing up front to identify these targetable mutations as early as possible,” he says. –Mitch Leslie
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