BACKGROUND: Capmatinib, a highly selective and potent MET inhibitor, was approved for patients (pts) with advanced MET exon 14 NSCLC in the US in 2020 based on the GEOMETRY mono-1 trial data. Subgroup analyses from that study showed intracranial (IC) efficacy in pts with BM. However, there were no data on the effectiveness of capmatinib in pts with BM in the real-world setting; IC effectiveness is particularly challenging to study as many pts are also treated with radiation therapy (RT) to the brain. The current study examined real-world clinical outcomes of pts with NSCLC with MET exon 14 skipping mutation and BM who were treated with capmatinib, including those who were RT-naïve.
METHODS: A retrospective medical record review was performed by panel-based oncologists recruited nationwide in the US. Eligible pts were aged ≥ 18 years, had confirmed BM diagnosis and MET exon 14 skipping mutated NSCLC, started capmatinib therapy in any line following BM diagnosis (with ≥ 1 IC lesion ≥ 10 mm), and had a follow up of ≥ 6 months after starting capmatinib (except death). Modified (pseudo) RECIST and RANO-BM criteria were used for response assessments. Key outcomes were IC and systemic real-world best overall response rate (rwORR), disease control rate (rwDCR), progression-free survival (rwPFS), and time-to-treatment discontinuation (TTD) assessed separately for first-line (1L) capmatinib and immunotherapy (IO)-containing regimens alone or in combination with chemotherapy (CT). The analyses are descriptive in nature. Outcomes were also analyzed in RT-naïve pts (no prior/concurrent BM RT).
RESULTS: A total of 68 eligible pt charts were abstracted (median age at BM diagnosis, 64.3 years; 60.3% male; 72.1% treated in academic setting; 83.8% de novo metastatic). For the 1L therapy after BM diagnosis, 80.9% (n = 55) received capmatinib, 16.2% (n = 11) received IO-containing regimens, and 2.9% received CT alone; 29 pts were RT-naive. The IC rwORR in RT-naïve pts was 85.0% for capmatinib 1L and 11.1% for IO 1L (Table). In the overall cohort, the IC rwORR was 87.3% (rwDCR 96.4%) for capmatinib 1L and 27.3% (rwDCR 45.5%) for IO 1L. Median systemic rwPFS was 14.1 months for capmatinib 1L and 5.1 months for IO 1L. The 1-year systemic rwPFS rate was 70.8% for capmatinib 1L and 18.2% for IO 1L. TTD was 13.2 months for capmatinib 1L and 5.1 months IO 1L.
CONCLUSIONS: This study shows a substantial systemic and IC effectiveness associated with capmatinib 1L use in pts with NSCLC with MET exon 14 and BM in the real-world setting. These findings remain true in RT-naïve pts.
