4285 - Radiosurgery followed by Tumor Treating Fields (TTFields) for brain metastases (1-10) from NSCLC in the phase 3 METIS trial

Background

Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising alternating electric fields. TTFields have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The METIS study [NCT02831959] investigates the efficacy and safety of TTFields in NSCLC patients with brain metastases.

Trial design

NSCLC patients (N = 270) with 1-10 brain metastases 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, while patients receive the best standard-of-care for their systemic disease. Patients are followed every two months until second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases 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 brain metastases 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 1–4 and 5–10 brain metastases; bi-monthly intracranial progression rate from 2–12 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. In August 2018, an independent Data Monitoring Committee (DMC) performed a review of the METIS trial data collected to that point. The DMC concluded that no unexpected safety issues have emerged on the study, and recommended to continue the METIS study as planned.

Clinical trial identification

NCT02831959.

Editorial acknowledgement

Legal entity responsible for the study

Novocure.

Funding

Novocure.

Disclosure

M. Mehta: Advisory / Consultancy: Varian Medical Systems ; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Celgene; Advisory / Consultancy: Tocagen; Advisory / Consultancy: AbbVie; Leadership role: Oncoceutics ; Shareholder / Stockholder / Stock options, Officer / Board of Directors: Pharmacyclics; Advisory / Consultancy: Cavion, Novocure, Varian, Agenus, Insys, Remedy, IBA. M. Ahluwalia: Advisory / Consultancy: Monteris Medical ; Advisory / Consultancy: AstraZeneca ; Advisory / Consultancy: Bristol-Myers Squibb ; Advisory / Consultancy: AbbVie; Advisory / Consultancy: CBT Pharmaceuticals; Advisory / Consultancy: Kadmon ; Advisory / Consultancy: VBI Vaccines ; Shareholder / Stockholder / Stock options: MimiVax ; Honoraria (self): Prime Oncology ; Research grant / Funding (institution): Novartis ; Research grant / Funding (institution): Novocure; Research grant / Funding (institution): Boehringer Ingelheim ; Research grant / Funding (institution): Aztra zeneca; Research grant / Funding (institution): Lilly/ImClone . P. Brown: Advisory / Consultancy: Novella Clinical. All other authors have declared no conflicts of interest.