Dr Kazmi Discusses the METIS Trial in NSCLC Patients with Brain Metastases
Presenter
Shayma Kazmi, MD, University of Pennsylvania
Conference
2024 ASCO Direct™ Philadelphia
The Bottom Line
The METIS trial investigated the use of tumor treating fields (TTFields) to improve intracranial disease control in patients with non-small cell lung cancer (NSCLC) who have developed brain metastases. Results from the trial showed that TTFields, a novel, non-invasive type of therapy, could significantly delay time to intracranial progression, as compared with supportive care alone, and highlight its potential as an adjunctive therapy to standard treatment for NSCLC patients with brain metastases. Dr. Shayma Kazmi emphasized that while this therapy requires substantial patient commitment, it may offer a valuable option for motivated individuals aiming to maintain their quality of life and prevent progression, while managing brain metastases.
Background
Brain metastases in NSCLC are common and can be challenging to treat, due to the limited efficacy of standard systemic therapies in the central nervous system (CNS). TTFields, a technology that delivers electric fields to disrupt cancer cell division, has shown efficacy in controlling primary brain tumors and certain types of brain metastases. The METIS trial sought to evaluate whether TTFields, when added as an adjunctive treatment after stereotactic radiosurgery (SRS), could further delay intracranial progression in NSCLC patients with brain metastases.
Trial Design and Patients
The METIS trial was a phase III study that included patients with 1 to 10 brain metastases from NSCLC, who were all suitable candidates for SRS. Patients in the trial were randomized to either receive TTFields therapy following SRS, or standard supportive care alone. Key inclusion criteria included a good performance status and the absence of leptomeningeal disease or prior use of whole-brain radiation therapy. The primary endpoint was the time to first intracranial progression, and additional evaluations included overall survival (OS) and quality of life (QoL) measures.
Main Trial Results
Results from METIS presented at this year’s Annual Meeting of the American Society for Clinical Oncology (ASCO) showed a benefit of TTFields adding in the following study endpoints:
Time to First Intracranial Progression: TTFields extended the median time to first intracranial progression to 10.6 months compared to supportive care alone, marking a statistically significant benefit. This indicates that TTFields can delay recurrence of brain metastases in patients with NSCLC.
Overall Survival: While the data for overall survival are not yet mature, TTFields’ impact on intracranial control suggests a potential benefit in delaying overall disease progression in the brain.
Quality of Life: Quality of life assessments showed that patients receiving TTFields maintained their overall global health status and physical functioning, with reduced fatigue and improved neurological stability. Dr. Kazmi noted that these results are encouraging, as they suggest TTFields do not negatively impact daily life despite the considerable demands of using the device.
Adverse Events and Tolerability
The primary adverse event associated with TTFields was mild to moderate skin irritation (grades 1–2) at the site of device attachment, experienced by about half of the patients. This skin reaction was attributed to the adhesive arrays used in the treatment. A small number of patients experienced grade 3 or higher skin toxicity, and there was one reported case of seizures attributed to disease progression. Overall, the TTFields therapy was well tolerated, with manageable side effects for motivated patients.
Conclusions and Faculty Insights
Dr. Kazmi highlighted that the TTFields therapy, though challenging in its practical application, offers a promising non-pharmacological intervention for brain metastases in NSCLC, particularly for patients seeking to avoid repeat brain radiation. She stressed that TTFields could be a practice-changing option for select patients willing to adhere to its requirements, which involve wearing the device for up to 18 hours daily. Dr. Kazmi noted that while TTFields may not be suitable for every patient, they represent a novel approach to managing brain metastases that could be valuable in highly motivated patients who prioritize CNS disease control and maintaining their quality of life.
Speaker Disclosure Information: Dr. Kazmi did not report any relevant disclosures for this presentation.