Capmatinib in Japanese patients with MET exon 14 skipping-mutated or MET-amplified advanced NSCLC: GEOMETRY mono-1 study.

Autor: Seto T; Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan., Ohashi K; Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan., Sugawara S; Sendai Kousei Hospital, Miyagi, Japan., Nishio M; Thoracic Center, Cancer Institute Hospital of JFCR, Tokyo, Japan., Takeda M; Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan., Aoe K; Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Yamaguchi, Japan., Moizumi S; Development Division, Novartis Pharma K.K., Tokyo, Japan., Nomura S; Development Division, Novartis Pharma K.K., Tokyo, Japan., Tajima T; Development Division, Novartis Pharma K.K., Tokyo, Japan., Hida T; Department of Thoracic Oncology, Aichi Cancer Center Hospital, Aichi, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2021 Apr; Vol. 112 (4), pp. 1556-1566. Date of Electronic Publication: 2021 Feb 24.
DOI: 10.1111/cas.14826
Abstrakt: MET mutations leading to exon 14 skipping (METΔex14) are strong molecular drivers for non-small-cell lung cancer (NSCLC). Capmatinib is a highly potent, selective oral MET inhibitor that showed clinically meaningful efficacy and a manageable safety profile in a global phase II study (GEOMETRY mono-1, NCT02414139) in patients with advanced METΔex14-mutated/MET-amplified NSCLC. We report results of preplanned analyses of 45 Japanese patients according to MET status (METΔex14-mutated or MET-amplified) and line of therapy (first- [1L] or second-/third-line [2/3L]). The starting dose was 400 mg twice daily. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee. A key secondary endpoint was duration of response (DOR). Among METΔex14-mutated patients, in the 1L group, one patient achieved partial response (DOR of 4.24 months) and the other had stable disease. In the 2/3L group, the ORR was 36.4% (95% confidence interval [CI] 10.9%-69.2%), median DOR was not evaluable, and progression-free survival was 4.70 months. One patient (2/3L group) showed partial resolution of brain lesions per independent neuroradiologist review. In MET-amplified patients with a MET gene copy number of ≥10, the ORR was 100% (2/2 patients) in the 1L group and 45.5% (5/11 patients) in the 2/3L group, with DOR of 8.2 and 8.3 months, respectively. Common treatment-related adverse events among the 45 Japanese patients were blood creatinine increased (53.3%), nausea (35.6%), and oedema peripheral (31.1%); most were grade 1/2 severity. In conclusion, capmatinib was effective and well tolerated by Japanese patients with METΔex14/MET-amplified NSCLC, consistent with the overall population.
(© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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