Work

Data from Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice

Year: 2023

Type: other

Abstract: Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non–small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups. Patients and Methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity. Results: 152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7–53.0]. Patients aged <75 (n = 84) and ≥75 (n = 68) had ORRs of 48.8% (95% CI: 37.7–60.0) and 39.7% (95% CI: 28.0–52.3), respectively. Treatment-naïve (n = 69) versus previously treated (n = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9–57.4) vs. 44.6% (33.7–55.9); median duration of response (95% CI): 10.8 (6.9–not estimable) vs. 11.1 (9.5–18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies. Conclusions: Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations. See related commentary by Rosner and Spira, p. 1055

DOI: 10.1158/1078-0432.c.6531026.v1

Institutions: The University of Texas MD Anderson Cancer Center, Saitama Cancer Center, Vall d'Hebron Institute of Oncology, Centre Hospitalier Universitaire de Bordeaux, University of Chicago, University of Chicago Medical Center, Fondazione IRCCS Istituto Nazionale dei Tumori, Antwerp University Hospital, Centre National de la Recherche Scientifique, Inserm, Université de Lille, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Centre de Recherches en Cancérologie de Lille, Instituto Oncológico Dr. Rosell, Hospital Universitario Dexeus, Centre Hospitalier Universitaire de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, The Netherlands Cancer Institute, Heidelberg University, German Center for Lung Research, Vanderbilt University Medical Center, Yonsei University, Yonsei Cancer Hospital, National Taiwan University, Taipei Veterans General Hospital, National Yang Ming University, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Samsung Medical Center, Sungkyunkwan University, Carl von Ossietzky Universität Oldenburg, Pius Hospital Oldenburg, Sarah Cannon, Tennessee Oncology, Meir Medical Center, University Hospital Zurich, Merck KGaA, Darmstadt (Germany), Merck Healthcare KGaA, Darmstadt (Germany), Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine

Language: English

Topic: Lung Cancer Treatments and Mutations

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Funder: Merck KGaA

Awards: G1670422463, G490769284

OpenAlex ID: W4361814326

Cites: 14

Cited by:

Related to: 10