Impact of MET inhibitors on survival among patients (pts) with MET exon 14 mutant (METdel14) non-small cell lung cancer (NSCLC).

Abstract

8511 Background: Dramatic responses to MET inhibitors have been reported in patients with NSCLC harboring activating mutations that cause MET exon 14 ( METdel14) skipping. We conducted a multicenter retrospective analysis of pts with METdel14 NSCLC to determine if treatment with MET inhibitors impacts survival. Methods: We collected clinicopathologic data on pts with METdel14 NSCLC. Event-time distributions were estimated using Kaplan-Meier and compared with the log-rank test. Multivariable Cox models were fitted to estimate hazard ratios. Results: Of the 148 pts with METdel14 mutant NSCLC, the median age was 72 (range 43-88); 57% were women, and 41% were never smokers. The most common histologies were adenocarcinoma (77%) and pulmonary sarcomatoid carcinoma (14%). Overlap with oncogenic driver mutations in other genes was rare. At the time of diagnosis, 70% of pts had stage I-III disease, and 30% had stage IV disease. Of the 34 pts with metastastic disease who never received a MET inhibitor, the median overall survival (mOS) was 8.1 months. In this cohort, cancers that also had concurrent MET amplification had a trend toward worse survival compared to cancers without MET amplification (5.2 months vs 10.5 months, P = 0.06). Of the 27 pts with metastatic disease who received at least one MET inhibitor (including crizotinib, glesatinib, capmatinib, and ABBV-399), the mOS was 24.6 months. A model adjusting for receipt of a MET inhibitor as first- or second-line therapy as a time-dependent covariate demonstrated that treatment with a MET inhibitor was associated with a significant prolongation in survival (HR 0.11, 95% CI 0.01-0.92, P = 0.04). Among 22 patients treated with crizotinib, the median progression-free survival (PFS) was 7.36 months. Conclusions: Forpts with METdel14 NSCLC, treatment with a MET inhibitor is associated with an improvement in overall survival. The prognosis of pts who never received treatment with a MET inhibitor appears to be poor, particularly among METdel14 cancers with concurrent MET amplification.