RBTT-05. TUMOR TREATING FIELDS AND RADIOSURGERY FOR SUPRA- AND/OR INFRATENTORIAL BRAIN METASTASES (1–10) FROM NSCLC IN THE PHASE 3 METIS STUDY

Abstract

BACKGROUND: Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising low intensity alternating electric fields. TTFields has demonstrated efficacy in non-small cell lung cancer (NSCLC) in in vitro and in vivo models, and in a phase I/II clinical study. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. This prospective, multicenter study [NCT02831959] investigated the efficacy, safety and neurocognitive outcomes of TTFields in NSCLC patients with brain metastases (BMs). METHOD(S): NSCLC patients (N=270) with 1-10 BMs are randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, > 18 hours/day) within 7 days of SRS or supportive care. The TTFields portable device delivers TTFields to the brain using 4 transducer arrays and allows normal daily activities. Patients receive the best standard-of-care for their systemic disease. Patients are followed every two months until second intracranial progression. Patients in the control arm could cross over to TTFields at the time of second intracranial progression. Key inclusion criteria: KPS 70, new diagnosis of 1 inoperable or 210 supraand/ or infratentorial BMs from NSCLC amenable to SRS; KPS 70; and optimal therapy for extracranial disease. Prior WBRT or surgical resection of metastases, a single resectable lesion or recurrent BMs were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 14 and 510 BMs; bi-monthly intracranial progression rate from 212 months; and time to second intracranial and distant progression. The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at a two sided alpha of 0.05 to detect a hazard ratio of 0.57.