Real-World Treatment Outcomes of MET Exon14 Skipping in Non-small Cell Lung Cancer: GFPC 03-18 Study

by Selleckchem | Sep 29 2023

Background: MET-targeted tyrosine kinase inhibitors (TKIs) demonstrated efficacy in advanced non-small cell lung cancer (aNSCLC) with MET exon14 skipping mutations (METexon14); yet, data on the management of these patients in clinical practice is sparse.

Objective: The aim of this study was to describe the management of METexon14 aNSCLC patients.

Patients and methods: This real-life, retrospective study analyzed the management of METexon14 aNSCLC. The primary endpoint was the median overall survival (mOS). Secondary endpoints were to assess investigator-progression-free survival (PFS) and mOS in different subgroups: patients treated with (a) crizotinib, regardless of treatment line; (b) anti-MET TKIs (crizotinib, tepotinib, capmatinib); and (c) immunotherapy.

Results: A total of 118 patients were included between December 2015 and January 1, 2020 in 13 centers. Median age was 73 years, 62.7% were female, 83.9% had adenocarcinoma, 92.4% at stage IV, and 27% had more than three metastatic sites. The majority of the patients (106, 89.8%) received at least one systemic treatment; 73% received at least one anti-MET TKI: crizotinib (68.6%), tepotinib (16%), capmatinib (10%). Only 10% received two anti-MET TKIs in their treatment sequences. With a median follow-up of 16 months (95% CI 13.6-29.7), mOS was 27.1 months (95% CI 18-31.4). There was no significant difference between mOS of patients treated and never treated with crizotinib, 19.7 (95% CI 13.6-29.7) and 28 (95% CI 16.4-NR) months, respectively (p = 0.16); mOS of the TKI cohort and of the TKI-naïve patient cohort were 27.1 (95% CI 18-29.7) and 35.6 (95% CI 8.6-NR) months respectively, with no significant difference (p = 0.7).

Conclusions: In this real-life study, there was no evidence of benefit in mOS with anti-MET TKIs.

Comments:

The results of this real-life, retrospective study suggest that there was no evidence of a survival benefit in terms of median overall survival (mOS) with anti-MET tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (aNSCLC) and MET exon14 skipping mutations (METexon14). The study included a total of 118 patients treated between December 2015 and January 1, 2020, across 13 centers.

The majority of the patients (89.8%) received at least one systemic treatment, and 73% received at least one anti-MET TKI, including crizotinib (68.6%), tepotinib (16%), and capmatinib (10%). Only 10% of the patients received two anti-MET TKIs in their treatment sequences. The median follow-up period was 16 months.

The primary endpoint, mOS, was found to be 27.1 months (95% CI 18-31.4) in the overall patient population. However, there was no significant difference in mOS between patients treated with crizotinib and those who were not (19.7 vs. 28 months, respectively, p = 0.16). Similarly, there was no significant difference in mOS between the TKI-treated cohort and the TKI-naïve patient cohort (27.1 vs. 35.6 months, respectively, p = 0.7).

These findings suggest that in the real-world setting, the use of anti-MET TKIs did not demonstrate a survival advantage in patients with METexon14 aNSCLC. It's important to note that this study is retrospective and real-life in nature, which may introduce certain limitations such as potential selection biases, variations in treatment regimens, and other factors that can influence outcomes. Further research is needed to evaluate the efficacy of anti-MET TKIs in this patient population.