Tumor treating fields therapy after stereotactic radiosurgery for brain metastases from non-small cell lung cancer: final results of the phase 3 METIS study
Purpose - Improved treatments for brain metastases from non-small cell lung cancer (NSCLC BM) are needed to prolong time to intracranial progression (TTIP) without increasing neurotoxicity. Tumor Treating Fields (TTFields), electric fields delivered via skin-based arrays that disrupt cancer cell div...
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| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Article (Journal) |
| Lenguaje: | inglés |
| Publicado: |
1 February 2026
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| In: |
International journal of radiation oncology, biology, physics
Year: 2026, Volumen: 124, Número: 2, Pages: 278-293 |
| ISSN: | 1879-355X |
| DOI: | 10.1016/j.ijrobp.2025.08.066 |
| Acceso en línea: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ijrobp.2025.08.066 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0360301625062170 
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| Notas de Autor: | Minesh P. Mehta, MD, Vinai Gondi, MD, Manmeet Singh Ahluwalia, MD, David Roberge, MD, Terence Tai Weng Sio, MD, MS, Daniel M. Trifiletti, MD, Thierry Muanza, MD, Ana Misir Krpan, MD, PhD, Zhengfei Zhu, MD, Naren R. Ramakrishna, MD, PhD, John B. Fiveash, MD, Philippe Metellus, MD, PhD, Jinming Yu, MD, Chiachien Jake Wang, MD, Julian Jacob, MD, PhD, Christian F. Freyschlag, MD, Tibor Csőszi MD, Andrea Salmaggi, MD , Alisa Taliansky, MD, Ana Lucas, MD, Jürgen Debus, MD, PhD, Paul D. Brown, MD, and Maciej Harat, MD |
| Sumario: | Purpose - Improved treatments for brain metastases from non-small cell lung cancer (NSCLC BM) are needed to prolong time to intracranial progression (TTIP) without increasing neurotoxicity. Tumor Treating Fields (TTFields), 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 to 10 newly diagnosed NSCLC BMs suitable for stereotactic radiosurgery (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. The primary endpoint was TTIP (Response Assessment in Neuro-Oncology Brain Metastases criteria). 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 (hazard ratio [HR], 0.72 [95% CI, 0.53-0.98]; Fine-Gray P = .044). Intracranial progression rates at months 2, 6, 12, and 24 were 13.6% versus 22.1% (P = .034), 33.7% versus 46.4% (P = .018), 46.9% versus 59.4% (P = .023), and 53.6% versus 65.2% (P = .031; post hoc). Time to distant intracranial progression favored TTFields therapy, although not statistically significantly (HR, 0.76 [95% CI, 0.51-1.12]; log-rank P = .165; post hoc). In patients receiving immune checkpoint inhibitors (n = 118), the delays in both TTIP (HR, 0.63 [95% CI, 0.39-1.0]; Cox P = .049; Fine-Gray P = .055) and time to distant intracranial progression (HR, 0.41 [95% CI, 0.21-0.81]; log-rank P = .0087, post hoc) were more pronounced. Device-related adverse events 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 BMs, including those receiving immune checkpoint inhibitor. |
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| Notas: | Online verfügbar 29 September 2025, Version des Artikels 14 January 2026 Gesehen am 24.04.2026 |
| Descripción Física: | Online Resource |
| ISSN: | 1879-355X |
| DOI: | 10.1016/j.ijrobp.2025.08.066 |