TTFields After SRS Prolongs Intracranial Response in Brain Metastatic NSCLC

The addition of tumor treating fields (TTFields) following stereotactic radiosurgery (SRS) prolonged the time to intracranial progression among patients with brain metastatic non–small cell lung cancer (NSCLC), according to results from the phase 3 METIS study (NCT02831959) presented in a plenary session at the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting.

Efficacy data from the trial revealed that for patients treated with TTFields and SRS (n = 149) vs SRS alone (n = 149), 44.3% and 63.8% of the respective groups experienced an intracranial progression event. Moreover, the 12- and 24-month intracranial progression rates in the respective arms were 46.9% (95% CI, 37.6%-55.6%) vs 59.4% (95% CI, 50.7%-67.0%) and 53.6% (95% CI, 44.0%-62.3%) vs 65.2% (95% CI, 56.5%-72.6%), respectively (HR, 0.72; 95% CI, 0.53-0.98; P =.039). This corresponded with a 28% relative risk reduction with TTFields.

Additional data revealed that between the 2 arms, a non-significant difference in overall survival (OS) and time to neurocognitive failure was observed. In the TTFields and control arms, the median OS was 11.3 months (95% CI, 8.6-13.8) vs 10.6 months (95% CI, 6.8-14.1; HR, 1.04; 95% CI, 0.76-1.43; P = .763). Furthermore, the median time to neurocognitive failure in the respective arms was 2.0 months (95% CI, 1.9-2.1) and 2.0 months (95% CI, 1.9-2.2), respectively (HR, 1.12; 95% CI, 0.72-1.74; P = .607). Additionally, the radiographic response rate was not significantly different between arms; the rates were 49.0% (95% CI, 38.6%-59.4%) vs 46.0% (95% CI, 37.0%-55.2%), respectively (P = .659).

“Treatment with TTFields therapy following SRS significantly prolonged time to intracranial progression, the primary end point, [in patients with brain metastatic NSCLC],” Vinai Gondi, MD, director of Radiation Oncology at Northwestern Medicine West Region and Proton Center and a clinical associate professor of Radiation Oncology at Northwestern University Feinberg School of Medicine, said in the presentation of the trial findings. “The benefit may in part be related to preventing distant intracranial progression, although this difference was not statistically significant.”

Patients with 1 to 10 brain metastases from NSCLC were enrolled and randomly assigned 1:1 to undergo SRS followed by TTFields at 150kHz or SRS alone. Follow-up occurred every 8 weeks, and following first intracranial progression, TTFields was continued, or salvage therapy was initiated. At second intracranial progression, patients underwent salvage therapy but had the option to crossover to the TTFields arm in the SRS alone arm.

Study enrollment occurred from October 2016 to March 2023 and included 78 sites across 13 countries. The median follow-up time was 8.6 months (range, 0.07-85.2).

Among patients in the TTFields and control arms, the median age was 63.0 years (range, 37-84) vs 64.0 years (range, 39-78), and most patients were male (59.1% vs 65.8%). Most patients had a Karnofsky performance score of 80 or higher (81.2% vs 81.9%) and had 1 to 4 brain metastases (78.5% vs 77.8%). The most prevalent pathological diagnosis for NSCLC was adenocarcinoma (75.2% vs 78.5%).

The primary end point of the trial was time to intracranial progression. Secondary end points included time to neurocognitive failure, OS, and radiologic response. Exploratory end points included health-related quality of life and time to distant intracranial progression based on independent radiologic review committee.

With the addition of immune checkpoint inhibition, the effect of TTFields became more pronounced regarding time to first intracranial progression (HR, 0.63; 95% CI, 0.39-1.00; P = .049) and time to distant intracranial progression (HR, 0.41; 95% CI, 0.21-0.81; P = .009). Additional findings showed that combining TTFields with SRS did not negatively affect health-related quality of life.

A similar incidence of adverse effects (AEs) was observed with TTFields therapy following SRS vs SRS alone; grade 1/2 AEs occurred in 28.7% vs 16.5% of the respective arms, and grade 3 or higher AEs occurred in 32.6% vs 29.1% of the respective arms. Furthermore, device-related AEs occurred in 50.4% of patients in the TTFields arms, with 1.6% experiencing grade 3 or higher AEs. Serious device-related AEs occurred in 1.6% of patients, and 5.4% of patients experienced AEs leading to device discontinuation; 1 death was reported.

Reference

Gondi V, Ahluwalia MS, Roberge D, et al. 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. Presented at: 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting; September 27-October 1, 2025; San Francisco, CA. Abstract LBA03.