WCLC 2019: First Results Reported From the National Lung Matrix Trial
Posted: Monday, September 30, 2019
According to findings from the National Lung Matrix Trial, patients with advanced non–small cell lung cancer (NSCLC) may benefit from stratified therapies targeted to cancer type or molecular makeup. The study’s objective is to identify promising drug-biomarker combinations that warrant further research. Gary William Middleton, MD, of the University of Birmingham, UK, presented the trial’s first results at the International Association for the Study of Lung Cancer (IASLC) 2019 World Conference on Lung Cancer (WCLC) in Barcelona (Abstract PL02.09).
In this ongoing, multicenter, parallel-group, open-label, phase II trial, 315 patients with advanced NSCLC were assigned to at least one of eight targeted drugs based on biomarker profiles. A Bayesian adaptive design was used to screen responses in patients comprising 22 molecularly defined cohorts and to determine the ability to predict probability of success in each cohort. Relevant clinical outcomes for single agent therapy were median progression-free survival over 3 months or a greater than 30% objective response rate and/or durable clinical benefit rate at 24 weeks.
The median progression-free survival for patients with a KRAS mutation receiving palbociclib was 5.4 months; however, those with a KRAS mutation and loss of STK11 had a median progression-free survival of 2.71 months, with an estimated durable clinical benefit rate of 27% with no objective response. For patients with squamous and nonsquamous NSCLC with loss of CDKN2A, the median progression-free survival was 4.46 months and 3.19 months, respectively. The researchers estimated a greater than 99% objective response rate for crizotinib in patients with ROS1-gene fusions and MET exon 14 skipping mutation but a less than 1% probability of success for patients with MET amplification.
For the four cohorts who received the AKT inhibitor capivasertib (including those with PIK3CA amplifications), the predicted durable clinical benefit rate was less than 15% for all arms. Recruitment of patients with a single LKB1 mutation to the mTOR inhibitor vistusertib arm was halted at interim analysis, but it continues for patients with an LKB1/KRAS double mutation. The responses to the MEK inhibitor selumetinib plus docetaxel in the treatment of adenocarcinomas with mutated NF1 also warrant further study.
Disclosure: The study authors’ disclosure information may be found at wclc2019.iaslc.org.