Tumor Treating Fields (TTFields) therapy after stereotactic radiosurgery for brain metastases from non-small cell lung cancer: final results of the phase 3 METIS study
- PMID: 41033612
- DOI: 10.1016/j.ijrobp.2025.08.066
Tumor Treating Fields (TTFields) therapy after stereotactic radiosurgery for brain metastases from non-small cell lung cancer: final results of the phase 3 METIS study
Abstract
Purpose: Improved treatments for brain metastases from non-small cell lung cancer (NSCLC BM) are needed to prolong time to intracranial progression without increasing neurotoxicity. TTFields, are electric fields delivered via skin-based arrays that disrupt cancer cell division, have demonstrated efficacy and safety in glioblastoma, NSCLC, and pancreatic cancer.
Methods and materials: In the phase 3 METIS trial (NCT02831959) adults with 1-10 newly-diagnosed NSCLC BM suitable for SRS receiving optimal therapy for extracranial disease were randomized 1:1 to SRS followed by TTFields (150 kHz) or SRS alone. Radiologic progression was assessed by an independent radiology review committee. Primary endpoint was time to intracranial progression (TTIP; RANO-BM). Secondary endpoints included overall survival, neurocognitive function, quality of life (QoL), and safety.
Results: Patients (N=298) were followed for a median of 8.6 (0.07-85.2) months. TTFields significantly delayed TTIP (HR 0.72 [95% CI 0.53-0.98]; Fine-Gray P=0.044). Intracranial progression rates at months 2, 6, 12, and 24 were 13.6% vs 22.1% (P=0.034), 33.7% vs 46.4% (P=0.018), 46.9% vs 59.4% (P=0.023), and 53.6% vs 65.2% (P=0.031; post hoc). Time to distant intracranial progression (TTDP) favored TTFields therapy, although not statistically significantly (HR 0.76 [0.51-1.12]; log-rank P=0.165; post-hoc). In patients receiving immune checkpoint inhibitors (ICI; n=118), the delays in both TTIP (HR 0.63 [0.39-1.0]; Cox P=0.049; Fine-Gray P=0.055) and TTDP (HR 0.41 [0.21-0.81]; log-rank P=0.0087, post-hoc) were more pronounced. Device-related AEs were mainly grade ≤2 skin events. TTFields did not cause QoL deterioration, and improvements in deterioration-free survival and time to deterioration of the global health status, physical functioning and fatigue domains were observed (post-hoc).
Conclusions: By significantly prolonging TTIP, without worsening QoL or cognitive function, TTFields after SRS is a new treatment option for patients with NSCLC BM, including those receiving ICI.
Copyright © 2025. Published by Elsevier Inc.
Conflict of interest statement
Disclosure of potential conflicts of interest Minesh P. Mehta: Consulting honoraria from GT Technologies, Chimerix, AIQ, Telix, Kazia Therapeutics, and Novocure (unrelated to this trial); Leadership Roles in NRG Oncology Brain Tumor Committee, NRG Oncology Board, NAPT Board, PCG Board, Mevion Technological Advisory Board, and Xcision Board Vinai Gondi: Advisory Board and honoraria from Servier and AstraZeneca; NIH Grant Funding (Small Business Innovation Research Grant) from ImmunoChem Therapeutics, LLC; Leadership Roles in NRG Oncology (Brain Tumor Committee and Investigator and Career Development Committee). Manmeet Singh Ahluwalia: Grants from Pfizer (institution); Consulting fees from Bayer, Xoft, Apollomics, Autem therapeutics, GT Medical Technologies, Modifi biosciences, Allovir, EquilliumBio, VBI Vaccines, Servier Pharmaceuticals, Incyte, and Recordati; Stock options for Mimivax, Bugworks, Trisalus Lifesciences, and LiveAI David Roberge: Research grants to institution from Novocure and AlphaTAU; Consultant for Novocure and Recordati; Advisory board for Novocure, Roche Canada, Servier Canada, AstraZeneca Canada, and Novartis; Meeting faculty for Novocure, Accuray, and Recordati; Leadership roles for CARO (President), CCTG (Co-chair CNS Disease Site Committee), and AFX Medical (interim CEO); Ownership equity in MisoChip, Croton Healthcare, and AFX Medical. Terence Tai Weng Sio: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novocure, Inc., MJH Life Sciences, and Catalyst Pharmaceutical Research LLC Daniel Michael Trifiletti: Support for the manuscript from Novocure (paid to institution); grants from Varian Medical and Florida Department of Health (paid to institution); royalties or licenses from Springer (unrelated); consulting fees from Servier and Boston Scientific (unrelated); board member of ISRS and IRRF Thierry Muanza: Research grant to institution from Jewish General Hospital, Lady Davis; Leadership roles for Brain Tumor Foundation of Canada (Advocacy Committee Member) and Canadian Clinical Trial Group (Member) Ana Misir Krpan: No conflict of interest to disclose Zhengfei Zhu: No conflict of interest to disclose Naren R Ramakrishna: Consulting fees from Evolent; leadership roles for Brain Tumor Foundation of Canada (Advocacy Committee member) and Canadian Clinical Trial Group (member) John B. Fiveash: Research grant to institution from Varian Philippe Metellus: No conflict of interest to disclose Jinming Yu: No conflict of interest to disclose Chiachien Jake Wang: No conflict of interest to disclose Julian Jacob: Advisory board for Servier and Janssen; speakers bureau for Brainlab; consulting honoraria from TheraPanacea; grants for congress registration from Qualimedis Christian F. Freyschlag: Advisory board and speakers bureau for Novocure (unrelated to METIS) Tibor Csőszi: No conflict of interest to disclose Andrea Salmaggi: No conflict of interest to disclose Alisa Taliansky: No conflict of interest to disclose Ana Lucas: Speaking fees from AstraZeneca and Zeiss Jürgen Debus: Grants/contracts from RaySearch Laboratories AB, Vision RT Limited, Merck Serono GmbH, Siemens Healthcare GmbH, PTW-Freiburg Dr. Pychlau GmbH, Accuray Incorporated; Leadership roles: CEO of HIT Betriebs GmbH, Board of Directors at Heidelberg University Hospital; Equipment received from Intra OP (experimental accelerator) Paul D. Brown: Honorarium from UpToDate® Maciej Harat: Speakers bureau for Brainlab and Servier
LinkOut - more resources
Full Text Sources
