53P - MET exon 14 skipping mutations in non-small cell lung cancer: Real-world data from the Italian biomarker ATLAS database

Background

MET exon 14 skipping mutation (METex14) is a rare alteration in non-small cell lung cancer (NSCLC). Here we report disease and patients characteristics, efficacy and tolerability of MET inhibitors among advanced METex14 NSCLC patients from the Italian real-world registry ATLAS.

Methods

Clinical, pathological and molecular data, treatment efficacy/tolerability outcomes were retrospectively collected from patients’ medical charts and electronic healthcare records from the ATLAS registry.

Results

From July 2020 to July 2023 a total of 146 METex14 advanced NSCLC patients were included across 27 Italian centers. Median age was 74 years old (range 46-92). Most patients were male (52%), with ECOG- PS <2 (72%) and adenocarcinoma subtype (83%). 24% had brain metastases. Overall, 56 (38%) patients were treated with capmatinib and 34 (23%) with tepotinib. Among patients treated with MET inhibitors, 29% and 52% of them received targeted treatment in 1^st and 2^nd line, respectively. Response rate (RR) was 37% (33% in previously treated and 46% in treatment-naïve patients) with a disease control rate of 62%. With a median follow up of 10.8 months, progression free survival (PFS) was 6.6 months (95% CI: 4.3-8.3). In patients receiving MET inhibitor in 1^st, 2^nd and further lines, PFS was 7.2 (95% CI: 4.3-10.4), 6.6 months (95% CI: 5.1-11.2) and 3.9 months (95% CI: 2.7-8.7), respectively. Overall survival was 10.7 months (95% CI: 7.2-19.3). In patients with measurable brain metastases (17 cases), the intracranial RR was 41%. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 12% of patients with grade 3 peripheral edema in 7% of cases. A fatal adverse reaction occurred in one patient due to pneumonitis. TRAEs-related dose reduction and discontinuation were reported in 6% and 8% of cases.

Conclusions

Capmatinib and tepotinib represent an effective treatment option in NSCLC patients with MET exon 14 skipping mutation. Real-world efficacy outcomes are worse than those reported in prospective clinical trials. MET inhibitor activity is more pronounced in the treatment-naïve population, suggesting that this is the right setting in the METex14 therapeutic strategy management.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Passiglia: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Novartis, Roche, MSD, Amgen, Janssen, Sanofi, BeiGene, Thermo Fisher Scientific. M. Occhipinti: Financial Interests, Personal, Other: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD. S. Pilotto: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Novartis, Amgen, Takeda, Sanofi, Bristol-Myers Squibb, MSD, Roche. E. Bria: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: MSD, Pfizer, Eli Lilly, BMS, Novartis, Takeda. S. Novello: Financial Interests, Personal, Invited Speaker: Eli Lilly, MSD, Roche, BMS, Takeda, Pfizer, AstraZeneca, Boehringer Ingelheim. M. Tiseo: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim. G. Pasello: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Roche, Lilly, MSD, Novartis, Amgen, Janssen. All other authors have declared no conflicts of interest.