Minesh Mehta, MD, Discusses the METIS Study of Tumor Treating Fields in NSCLC With Brain Metastases

Minesh P. Mehta, MD, of the Miami Cancer Institute at Baptist Health South Florida, discusses results from the METIS study that he presented during an oral abstract session at the 2024 American Society of Clinical Oncology Annual Meeting.

The METIS study met its primary end point, demonstrating that therapy with Tumor Treating Fields (TTFields) after stereotactic radiosurgery in patients with mutation-negative non-small cell lung cancer (NSCLC) and brain metastases can significantly prolong time to intracranial progression, Dr. Mehta said.

“The top line results show that there was a 10.6-month improvement in median time to intracranial progression or intracranial failure,” Dr. Mehta said. “This is a substantial improvement in the intracranial control rates on patients.”

It was important to evaluate TTFields in this population of patients because stereotactic radiosurgery is the “current preferred therapy” for patients with NSCLC and brain metastases, but “due to frequent intracranial failures, there is a high unmet need for salvage therapies,” Dr. Mehta explained in the abstract.

TTFields, which are “electric fields that disrupt cancer cell division” that have shown “improved survival and safety in patients with glioblastoma and metastatic NSCLC,” were investigated in the trial because whole-brain radiotherapy can be an option to reduce intracranial failure rates, but it is “used less frequently due to cognitive consequences,” according to Dr. Mehta.

The study included 298 patients with mutation-negative NSCLC who were newly diagnosed with 1 inoperable or 2 to 10 supra-/infratentorial brain metastases that were suitable for stereotactic radiotherapy and were receiving “optimal “extracranial disease therapy. All patients had a Karnofsky performance status of ≥70. Patients with prior whole-brain radiotherapy and a single operable or recurrent brain metastasis were excluded from the study. The median patient age was 63.5 years, with a median time of 1.8 months since NSCLC diagnosis. The most common NSCLC diagnosis was adenocarcinoma, reported in 77% of patients. Around one-third of patients were female (37.6%) and most patients had a Karnofsky performance status of ≥80.

The study investigators randomized patients 1:1 to receive stereotactic radiosurgery followed by 150 kHz of TTFields therapy with best supportive care or stereotactic radiosurgery followed by best supportive care. The baseline characteristics of patients were balanced between arms.

Patients received a median of 16 weeks of therapy with TTFields, with a median usage time of 67%. The primary end point, which was the time to intracranial progression since stereotactic radiosurgery, was significantly prolonged in patients who received TTFields and best supportive care after surgery (median, 21.9 months). The median time to intracranial progression since stereotactic radiosurgery was 11.3 months in patients in the other arm of the study (hazard ratio, 0.67; P=.02).

Adverse events related to TTFields were “mainly dermatological” and were grade 2 or less. In addition, the TTFields therapy also “improved deterioration-free survival of global health status, physical functioning, and fatigue according to [quality of life], and did not negatively impact cognition,” according to the trial investigators.

Reference

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. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.