Is MET Inhibition Billboard-Worthy for NSCLC?
Is MET Inhibition Billboard-Worthy for NSCLC?
Editor's Note: The MARQUEE trial, which looked at the combination of tivantinib and erlotinib in previously treated patients with non-small cell lung cancer (NSCLC), received mixed reviews. Much of the debate centered on MET inhibition and its potential benefit to patients with NSCLC. Medscape columnist H. Jack West, MD, recently spoke to Gregory J. Riely, MD, PhD, whose research focuses on specific mutations in NSCLC, about the MARQUEE trial, MET inhibition, and whether MET is potentially an important target in NSCLC.
Dr. West: The MARQUEE trial has been portrayed in news releases as both a negative trial and, with a little more fanfare, a positive trial, on the basis of progression-free survival (PFS) benefit in the overall study population as well as in the subset of patients with MET-positive disease. What is your take on the study?
Dr. Riely: The MARQUEE trial in some ways has very similar results to what we saw with the randomized phase 2 trial of tivantinib and erlotinib vs erlotinib alone. The phase 2 trial that served as the basis for MARQUEE did not show an overall positive result. There was no improvement in PFS and no improvement in overall survival (OS) for the total population.
Subset analyses were done, and the data that led to the MARQUEE phase 3 trial were from the subset of patients with NSCLC. That was a pretty broad population selected on the basis of the randomized phase 2 trial. The investigators could have taken a different approach and looked specifically at patients who were positive for MET by a diagnostic test. They had data from the randomized phase 2 trial, which showed that in patients with a FISH test that was positive for MET there was a much, much better signal in favor of the erlotinib/tivantinib combination.
Instead, the investigators chose to select a broader population to assess the hypothesis that MET plus EGFR [epidermal growth factor receptor] inhibition was better than EGFR inhibition alone. The results were negative in the overall population of patients with NSCLC, but when they looked at the diagnostic testing in terms of a MET-positive population, they did see significant benefit in that group of patients.
I think the suggestion was there in the phase 2 data, but they chose not to take that path and looked instead at the broader population.
MARQUEE Results: Were Expectations MET?
Editor's Note: The MARQUEE trial, which looked at the combination of tivantinib and erlotinib in previously treated patients with non-small cell lung cancer (NSCLC), received mixed reviews. Much of the debate centered on MET inhibition and its potential benefit to patients with NSCLC. Medscape columnist H. Jack West, MD, recently spoke to Gregory J. Riely, MD, PhD, whose research focuses on specific mutations in NSCLC, about the MARQUEE trial, MET inhibition, and whether MET is potentially an important target in NSCLC.
Dr. West: The MARQUEE trial has been portrayed in news releases as both a negative trial and, with a little more fanfare, a positive trial, on the basis of progression-free survival (PFS) benefit in the overall study population as well as in the subset of patients with MET-positive disease. What is your take on the study?
Dr. Riely: The MARQUEE trial in some ways has very similar results to what we saw with the randomized phase 2 trial of tivantinib and erlotinib vs erlotinib alone. The phase 2 trial that served as the basis for MARQUEE did not show an overall positive result. There was no improvement in PFS and no improvement in overall survival (OS) for the total population.
Subset analyses were done, and the data that led to the MARQUEE phase 3 trial were from the subset of patients with NSCLC. That was a pretty broad population selected on the basis of the randomized phase 2 trial. The investigators could have taken a different approach and looked specifically at patients who were positive for MET by a diagnostic test. They had data from the randomized phase 2 trial, which showed that in patients with a FISH test that was positive for MET there was a much, much better signal in favor of the erlotinib/tivantinib combination.
Instead, the investigators chose to select a broader population to assess the hypothesis that MET plus EGFR [epidermal growth factor receptor] inhibition was better than EGFR inhibition alone. The results were negative in the overall population of patients with NSCLC, but when they looked at the diagnostic testing in terms of a MET-positive population, they did see significant benefit in that group of patients.
I think the suggestion was there in the phase 2 data, but they chose not to take that path and looked instead at the broader population.