Tumor Treating Fields Therapy After Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer: Final Results of the Phase 3 METIS Study
Article
Mehta, MP, Gondi, V, Ahluwalia, MS et al. (2025). Tumor Treating Fields Therapy After Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer: Final Results of the Phase 3 METIS Study
. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 10.1016/j.ijrobp.2025.08.066
Mehta, MP, Gondi, V, Ahluwalia, MS et al. (2025). Tumor Treating Fields Therapy After Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer: Final Results of the Phase 3 METIS Study
. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 10.1016/j.ijrobp.2025.08.066
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.
