Efficacy and safety of crizotinib in patients (pts) with advanced MET exon 14-altered non-small cell lung cancer (NSCLC).

Lung Cancer—Non-Small Cell Metastatic
Session Type and Session Title: 
Clinical Science Symposium, Actionable Mutations Redefined
Abstract Number: 


J Clin Oncol 34, 2016 (suppl; abstr 108)
Alexander E. Drilon, D. Ross Camidge, Sai-Hong Ignatius Ou, Jeffrey William Clark, Mark A. Socinski, Jared Weiss, Gregory J. Riely, Maria Winter, Sherry C. Wang, Katherine Monti, Keith D. Wilner, Paul K. Paik; Memorial Sloan Kettering Cancer Center, New York, NY; University of Colorado, Aurora, CO; University of California at Irvine, Irvine, CA; Massachusetts General Hospital Cancer Center, Boston, MA; University of Pittsburgh Medical Center, Pittsburgh, PA; Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill, NC; Pfizer Oncology, La Jolla, CA; Rho Inc., Chapel Hill, NC

Abstract Disclosures


Background: MET alterations leading to exon 14 skipping occur in ~4% of lung carcinomas, resulting in MET activation and sensitivity to MET inhibitors in vitro. Crizotinib, initially developed as a MET inhibitor, is currently approved for the treatment of ALK-positive NSCLC. We present crizotinib antitumor activity and safety data in pts with advanced MET exon 14-altered NSCLC. Methods: Pts with MET exon 14-altered NSCLC were enrolled into an expansion cohort of the ongoing phase I PROFILE 1001 study (NCT00585195) and received crizotinib at a starting dose of 250 mg BID. Responses were assessed using RECIST v1.0. Results: As of the data cut-off of Oct 30, 2015, 18 pts with MET exon 14-altered NSCLC had enrolled and 17 received treatment (15 response-evaluable, 2 not yet evaluable). Two pts discontinued treatment (1 due to an AE, 1 preferred another treatment formulation). Median age was 68 y (range 59−87). Tumor histology was as follows: 71% adenocarcinoma, 18% sarcomatoid adenocarcinoma, 6% adenosquamous carcinoma, and 6% squamous cell carcinoma. 65% were former and 35% never-smokers. Duration of treatment ranged from 0.5 to 9.1+ mo, with 88% of pts (15/17) still ongoing. Evidence of antitumor activity per RECIST was documented in 10/15 pts: 5 with confirmed PRs (all seen at the first scheduled tumor assessment at 8 wk ± 1 wk) and 5 with unconfirmed PRs (3 pts remained evaluable). Median PFS could not be calculated, with no deaths or PD by the data cut-off. Treatment-related AEs (TRAEs) were reported in 82% of pts; the most common were edema (35%) nausea (35%), vision disorder (29%), bradycardia (24%), and vomiting (24%). Most TRAEs were grade 1/2 in severity. One grade 3 TRAE (edema) and no grade 4/5 TRAEs were reported. Accrual of pts with MET exon 14-altered NSCLC continues. Updated data with a cut-off of Feb 2016 will be presented. Conclusions: Crizotinib has antitumor activity in pts with MET exon 14-altered NSCLC. The drug has a generally tolerable AE profile, consistent with that previously reported for pts with ALK-positive or ROS1-rearranged NSCLC. Further study of crizotinib in this pt population is warranted. Clinical trial information: NCT00585195