TTFields Plus BSC Prolongs Time to Intracranial Progression in NSCLC Brain Metastases

Minesh Mehta, MD

The addition of tumor treating fields (TTFields) therapy to best supportive care (BSC) was well tolerated and significantly improved both time to first intracranial progression and deterioration-free survival vs BSC alone in patients with non–small cell lung cancer (NSCLC) and brain metastases, according to findings from the phase 3 METIS trial (NCT02831959) presented during the 2024 ASCO Annual Meeting.¹

Data showed that the median time to intracranial progression was 21.9 months vs 11.3 months, respectively, with the addition of TTFields to BSC vs BSC alone, translating to a statistically significant reduction in risk of 33% (HR, 0.67; P =.0158).

Patients treated with TTFields therapy also had an extended quality-of-life (QOL) deterioration-free survival. The median time to QOL deterioration-free survival was not reached in the TTFields vs 7.7 months in the control arm of BSC alone (P =.038).

The researchers also observed that the addition of TTFields to BSC led to significant improvements in the majority of scales and items assessed by the EORTC QLQ core questionnaire and BN20 patient questionnaires. Importantly, there was no evidence of cognitive decline in the TTFields therapy group compared with the control arm, suggesting that this treatment not only is beneficial, but also preserves cognitive function.

“The primary end point was met, significantly prolonging the time to first intracranial progression by 10.6 months…In addition, TTFields therapy also added to best supportive care following stereotactic radiosurgery in terms of improved deterioration-free survival, a measure of quality-of-life, and was well-tolerated,” said Minesh Mehta, MD, chief of radiation oncology and deputy director at Miami Cancer Institute, part of Baptist Health South Florida, during a presentation of the data at the ASCO annual meeting.

In the phase 3 METIS trial, 298 adult patients with 1-10 brain metastases from NSCLC were randomized following stereotactic radiosurgery (SRS) and treated with either TTFields therapy and BSC (n = 149) or BSC alone (n = 149). Supportive care consisted of a range of interventions, including corticosteroids, anti-epileptics, anticoagulants, and medications for pain or nausea management.

Patients in both study arms were eligible for systemic therapy for their NSCLC at the discretion of their treating physician. Enrollment was open to patients with Karnofsky performance status (KPS) ≥70, those who were newly diagnosed with 1 inoperable or 2-10 supra/infratentorial brain metastases suitable for SRS, and those receiving optimal extracranial disease therapy. However, patients with known tumor mutations for which targeted agents are available were not eligible for enrollment in the trial.

Patients were stratified by the number of brain metastases (1-4 or 5-10), prior systemic therapy, and tumor histology, and crossover to the TTFields arm was allowed after confirmation of second intracranial progression.

"The study was conducted at 78 sites that enrolled patients. Two hundred and ninety-eight patients were randomized. The study was conducted between October 2016 and March 2023. The cutoff date for these data is December 5, 2023,” added Mehta.

The median duration of TTFields therapy was 16 weeks (range, 0.1-193.1) and the median usage was 67% (range, 0.8-96.7), which was similar to what has previously been demonstrated in studies of TTFields. Baseline patient demographics and characteristics were well balanced between arms with the median age being 63.5 (range, 37-84) years, 37.6% of patients being female, most having a KPS ≥ 80 (38.6%), and 76.8% of patients having adenocarcinoma.

In addition to the primary end point of time to first intracranial progression, as measured from the date of first SRS treatment to intracranial progression or neurological death, whichever occurs first, investigators assessed the secondary end points of time to distant progression, time to neurocognitive failure, overall survival (OS), time to second intracranial progression, QOL and adverse events (AEs).

A preliminary analysis of key secondary end points did not show statistical significance. For patients given TTFields therapy with BSC, the median OS was 11.3 months (95% CI, 8.5-13.5) compared with 10.6 months (95% CI, 6.8-14.1) in patients treated with BSC alone (P = .78). Full analysis of secondary end points, including time to neurocognitive failure, OS, and radiological response rate, is ongoing and will be reported at a later date.

For safety, 66 (52%) of the patients treated with TTFields had any-grade device-related AEs, most of which were skin-related. While the majority were grades 1 and 2, there were 3 (2.4%) patients who had grade ≥3 device-related AEs, 1 of which was grade 5 (seizures/tumor progression). Fifteen patients crossed over to receive TTFields therapy and of these patients, 1 had a device-related grade 3 AE, which was headache.

Moreover, the incidence of grade ≥3 serious AEs was comparable between the treatment arms at 63 patients (49.6%) in the TTFields arm vs 87 patients (54.4%) in the BSC alone arm.

“Please note that these are only the topline results and remaining detailed analysis for the rest of the data are ongoing. Based on these data, consideration should be given to TTFields as a potential adjunctive treatment to stereotactic radiosurgery in patients with non–small cell lung cancer without targetable oncogenic driver mutations,” concluded Mehta.

References

1. Mehta MP, Gondi V, Ahluwalia MS, et al. Results from METIS (EF-25), an international, multicenter phase III randomized study evaluating the efficacy and safety of tumor treating fields (TTFields) therapy in NSCLC patients with brain metastases. J Clin Oncol. 2024;42 (suppl 16;abstr 2008). doi:10.1200/JCO.2024.42.17_suppl.2008
2. METIS phase 3 clinical trial met primary endpoint significantly delaying time to intracranial progression with improved quality of life deterioration-free survival. News release. Novocure. June 3, 2024. Accessed June 3, 2024. https://tinyurl.com/bddrpkjd