Abstract CT151: TTFields and radiosurgery for 1 to 10 brain metastases from NSCLC in the phase III METIS study

Abstract

Abstract Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality, based on low intensity alternating electric fields. Efficacy of TTFields in non-small cell lung cancer (NSCLC) has been demonstrated in multiple 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 patients. The study [NCT02831959] objectives are to test the efficacy, safety and neurocognitive outcomes of TTFields in this patient population. Patients (N=270) with 1-10 brain metastases (BM) from NSCLC are randomized 1:1 to stereotactic radio surgery (SRS) followed by TTFields or supportive care. Patients are followed-up every two months until 2nd intracranial progression. Patients in the control arm may cross over to TTFields at the time of 2nd intracranial progression. Key inclusion criteria: KPS ≥70, 1 inoperable or 2-10 brain lesions amenable to SRS, optimal standard therapy for the extracranial disease, no brain-directed therapy, no signs of significantly increased intracranial pressure, and no electronic implantable devices in the brain. Endpoints included time to 1st intracranial progression or neurological death (primary); time to neurocognitive failure, HVLT, COWAT and TMT); overall survival; radiological response rate; quality-of-life; and adverse events. Treatment comprised continuous TTFields at 150 kHz for > 18 hours/day applied to the brain within 7 days of SRS. The treatment system is a portable medical device allowing normal daily activities. The device delivers TTFields to the brain using 4 Transducer Arrays, which may be covered by a wig or hat. Patients receive the best standard of care for their systemic disease. Statistical Considerations: This is a prospective, randomized, multicenter study. 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. Citation Format: Minesh Mehta, Vinai Gondi, Manmeet Ahluwalia,, Paul D. Brown. TTFields and radiosurgery for 1 to 10 brain metastases from NSCLC in the phase III METIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT151.