TTFields Meets Time to Intracranial Progression End Point in NSCLC Brain Metastases

Treatment with tumor treating fields (TTFields; NovoTTF-200M) plus supportive care led to a statistically significant improvement in time to intracranial progression compared with supportive care alone in patients with 1 to 10 brain metastases from non–small cell lung cancer (NSCLC) following stereotactic radiosurgery (SRS), meeting the primary end point of the phase 3 METIS trial (NCT02831959).

Findings showed that patients treated with TTFields plus supportive care experienced a median time to intracranial progression of 21.9 months compared with 11.3 months for patients treated with supportive care alone (HR, 0.67; P = .016). Furthermore, the median TTFields treatment duration was 16 weeks, and the median usage was 67%.

In an announcement of the data, Novocure said it plans to present these findings to regulatory agencies, publish the results in a peer-reviewed journal, and present them at an upcoming medical conference.

“Patients with brain metastases from NSCLC are frequently treated with radiosurgery but face a high likelihood of rapid brain relapse,” Minesh Mehta, MD, deputy director and chief of Radiation Oncology at Baptist Health Miami Cancer Institute, in Florida, stated in a news release. “In this international, multicenter, phase 3 trial, the use of TTFields therapy significantly delayed time to brain relapse, with associated improvement in quality of life and stable cognition. This is a major benefit and is potentially practice changing.”

The prospective, randomized, controlled trial of SRS with or without TTFields enrolled patients with 1 to 10 brain metastases stemming from NSCLC. A total of 298 eligible adult patients were enrolled, and after receiving SRS, they were randomly assigned to receive TTFields with supportive care or supportive care alone. Patients in the control arm had the option to switch to the TTFields arm upon confirmation of second intracranial progression.

Patients were stratified by the number of brain metastases (1-4 vs 5-10), prior systemic therapy, and tumor histology.

Supportive care included steroids, anti-epileptic drugs, anticoagulants, and medications for pain or nausea control. Both groups in the study were permitted to receive systemic therapy for their NSCLC as decided by their treating physician. Notably, those with actionable tumor mutations were not eligible for enrollment onto the trial.

The primary end point of the trial was time to first intracranial progression, as measured from the date of first SRS treatment to intracranial progression or neurological death per response assessment in neuro-oncology brain metastases (RANO-BM) criteria. Time to intracranial progression was calculated by cumulative incident function, and patient scans were evaluated by a blinded independent radiologic review committee.

Key secondary end points included time to distant progression, time to neurocognitive failure, overall survival (OS), time to second intracranial progression, quality of life (QOL), and adverse effects.

At the time of this analysis, key secondary end points, including time to neurocognitive failure, OS, and radiological response rate, did not reach statistical significance. However, some secondary end points, including time to distant progression and QOL, showed trends favoring TTFields. A full analysis of secondary end points is ongoing.

TTFields was well-tolerated with sustained QOL and neurocognitive function, which was consistent with data from previous studies. Notably, baseline characteristics were well balanced between arms.

“Novocure’s willingness to pursue areas of considerable unmet need, like the patient population studied in METIS, is a point of pride for our company,” Asaf Danziger, chief executive officer of Novocure, stated in a press release. “We are so pleased with the positive outcome of this trial and encouraged by TTFields’ performance. I would like to thank everyone involved with METIS, especially our courageous patients and dedicated investigators, for their contributions to the trial and for meaningfully contributing to the evolution of the treatment of brain metastases from NSCLC.”

Reference

METIS phase 3 clinical trial met primary endpoint, demonstrating a statistically significant extension in time to intracranial progression for patients with brain metastases from non–small cell lung cancer. News release. Novocure. March 27, 2024. Accessed March 27, 2024. https://www.novocure.com/metis-phase-3-clinical-trial-met-primary-endpoint-demonstrating-a-statistically-significant-extension-in-time-to-intracranial-progression-for-patients-with-brain-metastases-from-non-small-cell-lung-c/