MET exon 14 splice sites mutations define a unique subset of NSCLC patients who may benefit from MET inhibitors. Patterns of disease spread and response to chemotherapy in these patients are still poorly known.
Clinicopathologic characteristics and outcome of patients harboring MET exon 14 splice sites mutations identified in a single molecular center were retrospectively collected.
We identified 39 patients from 12 french institutions between July 2009 and February 2018. Median age was 75 (range 55-91), sex ratio was 1.16 (M/W), 15 patients (38%) were never smokers. histologic type was adenocarcinoma in 31 tumors (79%) pulmonary sarcomatoid carcinoma in 3 tumors (8%) and NOS NSCLC in 5 tumors (13%). MET exon 14 alterations were deletions in 21 patients (54%), point mutations in 14 patients (36%) and delins in 4 patients (10%). Ten patients had a concurrent TP53 mutation, 3 patients had a RAS mutation, and 1 patient had a PIK3CA mutation. Among the 14 patients tested for PDL1 expression, 9 (64%) were PDL1 high (≥50%). The disease was diagnosed at stage IIIB/IV in 24 patients (62%) . Among those, the most frequent metastatic sites at diagnosis were bones (61%), lung (43%), pleura (39%) and brain (13%). 17 patients received at least one line of chemotherapy. Objective response rate for 1st line chemotherapy was 44%. Anti-PD1 agent was initiated in 6 patients, 1 patient (16%) achieved an objective response. MET TKI was initiated in 7 patients. Median overall survival for stage IIIB/IV patients was 8.5 months.
NSCLC patients harboring a MET exon 14 splice sites mutation are characterized by older age, never smoking status in half of the cases, and metastatic spread to bones. Future efforts should focus on identifying predictive markers of response to MET TKIs.
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P. Jamme: Travel, Accommodations, Expenses: Chugai Pharma; Consulting: Boehringer Ingelheim International. C. Descarpentries: Personal fees: Roche, AstraZeneca and Boehringer. E. Dansin: Honoraria: BMS, MSD, AstraZeneca, Lilly and Roche (research support 2014). S. Baldacci: Personal fees: Lilly, GSK, Pfizer, Roche for activities outside the written work. A. Cortot: Travel, Accommodations, Expenses: AstraZeneca, Pfizer, Roche; Consulting for Boehringer Ingelheim International, Pfizer, Roche, MSD, AstraZeneca; Honoraria: Takeda, BMS; Research funding: Merck, Novartis. All other authors have declared no conflicts of interest.