Novocure's TTFields Therapy Significantly Delays Brain Metastasis Progression in NSCLC Patients Following Stereotactic Radiosurgery
核心洞察
The Phase 3 METIS trial demonstrated that TTFields therapy combined with best supportive care reduced the risk of intracranial progression by 28% compared to best supportive care alone in NSCLC patients with brain metastases.
Patients receiving TTFields therapy achieved a median time to intracranial progression of 15.0 months versus 7.5 months for the control group, with 2-year progression rates of 53.6% versus 65.2% respectively.
The treatment showed enhanced benefits in patients receiving immune checkpoint inhibitors, with no negative impact on quality of life or neurocognitive function.
The pivotal Phase 3 METIS trial has demonstrated that Novocure (搜索)'s Tumor Treating Fields (TTFields) therapy significantly delays brain metastasis progression in non-small cell lung cancer (NSCLC) patients when added to standard care following stereotactic radiosurgery. The results, published in the International Journal of Radiation Oncology Biology and Physics and presented at the 2025 ASTRO Annual Meeting, represent a potential breakthrough for patients facing one of cancer's most challenging complications.
Trial Design and Patient Population
The METIS trial enrolled 298 adult patients with 1-10 brain metastases from NSCLC, randomized to receive either TTFields therapy plus best supportive care (n=149) or best supportive care alone (n=149) following stereotactic radiosurgery of their brain metastases. The primary endpoint measured time to intracranial progression from the date of first SRS treatment to intracranial progression or neurological death.
Significant Reduction in Disease Progression
When accounting for competing risks using the Fine-Gray method, patients treated with TTFields therapy and best supportive care experienced a 28% lower risk of intracranial progression compared to those receiving best supportive care alone (HR 0.72, p=0.044). The median time to intracranial progression was 15.0 months in the TTFields group compared to 7.5 months in the control group.
The benefits were evident across multiple time points. At 2 months, patients treated with TTFields therapy had a 13.6% progression rate compared to 22.1% in the control group (p=0.034). This advantage persisted at 6 months (33.7% vs 46.4%, p=0.018), 12 months (46.9% vs 59.4%, p=0.023), and 24 months (53.6% vs 65.2%, p=0.031).
Enhanced Benefits with Immunotherapy
Among the 118 patients in the TTFields group who received immune checkpoint inhibitors for their primary disease during the study, the beneficial effects were more pronounced. These patients showed a hazard ratio of 0.63 for time to intracranial progression and 0.41 for time to distant intracranial progression.
"The METIS trial, demonstrating that the addition of Tumor Treating Fields following stereotactic radiosurgery delays brain metastasis progression with no negative impact on quality of life or neurocognition, is a pivotal and practice-impacting step forward in providing patients with a new treatment option," said Vinai Gondi, MD, Director of Radiation Oncology in the Northwestern Medicine West Region and Proton Center.
Safety and Quality of Life Profile
TTFields therapy demonstrated a favorable safety profile consistent with previous clinical trials. Grade 1/2 skin issues were the most common device-related adverse events. Importantly, the treatment did not cause quality of life deterioration overall, with improvements observed in deterioration-free survival and time to deterioration of global health status, physical functioning, and fatigue domains.
The median duration of TTFields therapy was 16 weeks with a median usage of 67%. There was no significant difference in secondary endpoints including neurocognitive failure, overall survival, or radiological response of brain lesions.
Addressing an Unmet Medical Need
"Lung cancer patients with brain metastases are living longer due to improved systemic therapies, bringing to the forefront an unmet need for well-tolerated treatment options that provide more durable control of brain metastases," noted Dr. Gondi.
Nicolas Leupin, MD, PhD, Chief Medical Officer at Novocure (搜索), emphasized the clinical significance: "When Tumor Treating Fields therapy was used to treat patients in the METIS trial, we saw a significant delay in the progression of intracranial metastases without adding systemic toxicity or causing neurocognitive side effects associated with other current treatments."
Regulatory Path Forward
Based on these results, Novocure (搜索) plans to submit a premarket approval application to the FDA for the treatment of adult patients with brain metastases from non-small cell lung cancer in the coming weeks. The company's TTFields technology uses electric fields to exert physical forces that kill cancer cells through multiple mechanisms while sparing healthy cells due to their different properties including division rate, morphology, and electrical characteristics.