Tumor Treating Fields (TTFields) therapy after stereotactic radiosurgery for brain metastases from non-small cell lung cancer: final results of the phase 3 METIS study
Mené sur 298 patients présentant 1 à 10 métastases cérébrales ayant pour origine un cancer du poumon non à petites cellules (durée médiane de suivi : 8,6 mois), cet essai randomisé de phase III évalue l'intérêt, du point de vue du délai de progression intracrânienne, d'ajouter un traitement par application de champs électriques à la radiochirurgie
Purpose: Improved treatments for brain metastases from non-small cell lung cancer (NSCLC BM) are needed to prolong time to intracranial progression without increasing neurotoxicity. TTFields, are electric fields delivered via skin-based arrays that disrupt cancer cell division, have demonstrated efficacy and safety in glioblastoma, NSCLC, and pancreatic cancer.
Methods and Materials: In the phase 3 METIS trial (NCT02831959) adults with 1–10 newly-diagnosed NSCLC BM suitable for SRS receiving optimal therapy for extracranial disease were randomized 1:1 to SRS followed by TTFields (150 kHz) or SRS alone. Radiologic progression was assessed by an independent radiology review committee. Primary endpoint was time to intracranial progression (TTIP; RANO-BM). Secondary endpoints included overall survival, neurocognitive function, quality of life (QoL), and safety.
Results: Patients (N=298) were followed for a median of 8.6 (0.07–85.2) months. TTFields significantly delayed TTIP (HR 0.72 [95% CI 0.53–0.98]; Fine-Gray P=0.044). Intracranial progression rates at months 2, 6, 12, and 24 were 13.6% vs 22.1% (P=0.034), 33.7% vs 46.4% (P=0.018), 46.9% vs 59.4% (P=0.023), and 53.6% vs 65.2% (P=0.031; post hoc). Time to distant intracranial progression (TTDP) favored TTFields therapy, although not statistically significantly (HR 0.76 [0.51–1.12]; log-rank P=0.165; post-hoc). In patients receiving immune checkpoint inhibitors (ICI; n=118), the delays in both TTIP (HR 0.63 [0.39–1.0]; Cox P=0.049; Fine-Gray P=0.055) and TTDP (HR 0.41 [0.21–0.81]; log-rank P=0.0087, post-hoc) were more pronounced. Device-related AEs were mainly grade ≤2 skin events. TTFields did not cause QoL deterioration, and improvements in deterioration-free survival and time to deterioration of the global health status, physical functioning and fatigue domains were observed (post-hoc).
Conclusions: By significantly prolonging TTIP, without worsening QoL or cognitive function, TTFields after SRS is a new treatment option for patients with NSCLC BM, including those receiving ICI.
International Journal of Radiation Oncology, Biology, Physics , article en libre accès, 2025