TTFields After Stereotactic Radiosurgery Improve Time to Progression Among Patients With Non-Small Cell Lung Cancer Brain Metastases
According to the phase 3 METIS trial, there was a statistically significant delay in time to first intracranial progression with tumor treating fields (TTFields) therapy, electric fields delivered via scalp-placed arrays that disrupt cancer cell division,” after stereotactic radiosurgery among patients with brain metastases from non-small cell lung cancer (NSCLC).
These data were first presented by Vinai Dongi, MD, Northwestern Medicine Warrenville Cancer Center and Proton Center, Warrenville, Illinois, at the American Society for Radiation Oncology (ASTRO) Annual Meeting in San Francisco, California.
According to Dr Gondi and coauthors, “intracranial progression after resection or [stereotactic radiosurgery] is more frequent than with WBRT [whole brain radiotherapy], but WBRT causes more neurotoxicity and neurocognitive decline.”
This phase 3 trial enrolled 298 patients with 1 to 10 newly diagnoses NSCLC brain metastases eligible for stereotactic radiosurgery and receiving optimal therapy for extracranial disease. Patients were randomized on a 1-to-1 basis to receive stereotactic surgery either alone or followed by either TTFields. Radiographic progression was assessed by blinded independent radiology review committee. The primary end point was time to intracranial progression (TTIP) with secondary end points including time to progression, neurocognitive function, overall survival (OS), quality of life, and safety.
The median duration of therapy with TTFields was 15.7 weeks, with median monthly usage of 67.1%. There was a significant delay in time to first intracranial progression from stereotactic radiosurgery with TTFields (hazard ratio [HR], 0.72; P = .044). The 2-month intracranial progression rates were 13.6% and 22.1% in the TTFields and stereotactic surgery alone arms respectively. The 6-month rates were 33.7% vs 46.4% (P = .034); 12-month were 46.9% vs 59.2% (P = .023); 24-month were 53.6% vs 65.2% (P = .031, post hoc). The TTIP benefit was more pronounced among patients who received immune checkpoint inhibitors for their primary disease (HR, 0.63; Cox P = 0.49). Overall, there was no difference in the time to progression. However, among patients receiving immune checkpoint inhibitors, TTFields delayed time to progression when compared to stereotactic surgery alone (HR, 0.41; Cox P = .009). There was no significant differences in time to neurocognitive failure, OS, or radiological response rate.
Adverse events related to TTFields were mainly grade 2 skin events. There was no quality-of-life degradation with TTFields, and there were improvements observed in deterioration-free survival and time to deterioration of global health status, physical functioning, and fatigue.
Dr Gondi et al, concluded, “By significantly prolonging time to intracranial progression, without deteriorating [quality of life] or cognitive function, TTFields therapy after [stereotactic radiosurgery] is a potential new treatment option” for patients with brain metastases from NSCLC. In a press release from Novocure, Dr Gondi added this trial “is a pivotal and practice-impacting step forward in providing patients with a new treatment option.”
Sources:
Gondi V, Ahluwalia M, Roberge D, et al. Tumor treating fields (TTFields) after stereotactic radiosurgery (SRS) for brain metastases from non-small cell lung cancer (NSCLC BM): Final results of the phase 3 METIS trial. Presented at ASTRO Annual Meeting. September 27-October 1, 2025; San Francisco, CA. LBA 03.
Novocure to present final results from the pivotal phase 3 METIS trial of its tumor treating fields (TTFields) therapy for brain metastases from non-small cell lung cancer at 2025 ASTRO Annual Meeting. Novocure. Published September 29, 2025. Accessed September 30, 2025. https://www.novocure.com/novocure-present-final-results-pivotal-phase-3-metis-trial-its-tumor-treating-fields-ttfields
