Abstract 1258P
Background
MET targeted tyrosine kinase inhibitors (TKI) demonstrated efficacy in advanced non-small cell lung cancer (aNSCLC) with METexon 14 skipping mutation (METexon14). Different variants of this mutation exist. Some do not affect the splice sites and may result in incomplete exon 14 skipping. This could explain a different anti-tumor activity of TKI.Functional analysis could specify if the exon skipping is effective.
Methods
AFonMET was a real-life, retrospective study of the management of METexon14 aNSCLC. Primary endpoint was the median overall survival (mOS) of patients treated with crizotinib and no other TKI (CRIZO-cohort). We also assessed mOS of patients treated with at least one anti-MET TKI (TKI-cohort) and the anti-tumor activity of crizotinib according to functional analyses results.
Results
106 treated patients were included between December 2015 and June 2019 in 13 centers: median age 72 years, female: 63%, adenocarcinoma: 86%, stage IV: 92%, more than 3 metastatic sites: 24%. 73% received at least one anti-MET TKI: crizotinib: 70%, tepotinib: 28%, capmatinib: 14%; 10% received two anti-MET TKIs in their treatment sequences. With a median follow-up of 16 months, mOS of the CRIZO-cohort was 19.7 (CI95%, 13.6-29.7) months. mOS of patients never treated with crizotinib was 28 (CI95%, 16.4-NR) months. There was no significant difference between these two cohorts (p= 0.16). mOS of the TKI-cohort and of the TKI-naïve patient cohort were 27.1 (CI95%, 18-29.7) months and 35.6 (CI95%, 8.6-NR) months respectively, with no significative difference (p= 0.7). 39 (73.6%) patients treated with crizotinib had a complete exon 14 skipping variant (group 1) and 8 (15.1%) a partial exon skipping variant (group 2). Duration of treatment and overall response rate with crizotinib were not statistically different between groups: 5.2 (CI95% 2.5-8.2) vs 5.6 (CI95% 0.9-22.3) months (p=0.6), and 53.8% vs 50% respectively.
Conclusions
In this real-life study, there was no evidence of benefit in OS with anti-MET TKIs. Functional analyses of MET exon 14 variants does not predict better efficacy of crizotinib. An update of the data will be presented at the congress.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
GFPC.
Funding
GFPC.
Disclosure
R. Veillon: Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AZ; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AbbVie. F. Guisier: Financial Interests, Personal, Expert Testimony: BMS; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: MSD; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Personal, Expert Testimony: Boehringer Ingelheim; Financial Interests, Personal, Expert Testimony: AstraZeneca. C. Decroisette: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Sandoz. A.B. Cortot: Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: AZ; Financial Interests, Personal, Expert Testimony: BI; Financial Interests, Personal, Expert Testimony: BMS; Financial Interests, Personal, Expert Testimony: MSD; Financial Interests, Personal, Expert Testimony: Merck; Financial Interests, Personal, Expert Testimony: Pfizer; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: Takeda. C. Chouaid: Financial Interests, Personal, Expert Testimony: AZ; Financial Interests, Personal, Expert Testimony: BI; Financial Interests, Personal, Expert Testimony: GSK; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Expert Testimony: Aventis; Financial Interests, Personal, Expert Testimony: BMS; Financial Interests, Personal, Expert Testimony: MSD; Financial Interests, Personal, Expert Testimony: Lilly; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Expert Testimony: Pfizer; Financial Interests, Personal, Expert Testimony: Janssen; Financial Interests, Personal, Expert Testimony: Takeda; Financial Interests, Personal, Expert Testimony: Amgen. R. Descourt: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis. All other authors have declared no conflicts of interest.