LBA 03 - Tumor Treating Fields (TTFields) After Stereotactic Radiosurgery (SRS) for Brain Metastases from Non-Small Cell Lung Cancer (NSCLC BM): Final Results of The Phase 3 METIS Trial
Presenter(s)
V. Gondi1, M. Ahluwalia2, D. Roberge3, R. Ilic4, T. T. W. Sio5, D. M. Trifiletti6, T. M. Muanz7, A. M. Krpan8, Z. Zhu9, N. R. Ramakrishna10, J. B. Fiveash11, P. B. Metellus12, C. J. Wang13, J. Jacob14, J. Yu15, C. F. Freyschlag16, T. Csoszi17, P. D. Brown18, M. Harat19,20, and M. P. Mehta2,21; 1Northwestern University Feinberg School of Medicine, Chicago, IL, 2Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 3Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada, 4Clinical Centre of Serbia, Beograd, Serbia, 5Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, 6Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, 7McGill University, Montreal, QC, Canada, 8Specialty Hospital Radiochirurgia Zagreb, Sveta Nedelja, Croatia, 9Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 10Department of Radiation Oncology, Orlando Health Cancer Institute, Orlando, FL, 11University of Alabama at Birmingham School of Medicine, Birmingham, AL, 12Private Hospital Clairval, Marseilles, France, 13Willis-Knighton Cancer Center, Shreveport, LA, 14University Hospitals Pitié-Salpêtrière, Paris, France, 15Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 16Medical University of Innsbruck, Innsbruck, Austria, 17Semmelweis University, Budapest, Hungary, 18Mayo Clinic Cancer Center, Rochester, MN, 19Bydgoszcz University of Science and Technology, Bydgoszcz, Poland, 20Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland, 21Herbert Wertheim College of Medicine, Florida International University, Miami, FL
Purpose/Objective(s):
Local therapy for NSCLC BM includes resection, SRS and whole brain radiotherapy (WBRT). Intracranial progression after resection or SRS is more frequent than with WBRT, but WBRT causes more neurotoxicity and neurocognitive decline. Delaying intracranial failure while preserving neurocognition is an unmet need. TTFields, electric fields delivered via scalp-placed arrays that disrupt cancer cell division, have demonstrated efficacy in glioblastoma, NSCLC and pancreatic cancer.Materials/Methods:
In the METIS trial (NCT02831959), adults with 1–10 newly diagnosed NSCLC BM suitable for SRS and receiving optimal therapy for extracranial disease were eligible. Prior WBRT, presence of known druggable mutations, single operable or recurrent BM were exclusion criteria. Patients (pts) were randomized 1:1 to SRS followed by TTFields therapy (150 kHz) or SRS alone. A blinded independent radiology review committee assessed radiographic progression. The primary endpoint of time to intracranial progression (TTIP, RANO-BM) was analyzed using cumulative incidence competing risk and Fine-Gray test to determine a difference. Secondary endpoints included time to distant progression (TTDP), neurocognitive function, overall survival (OS), quality of life (QoL) and safety.Results:
The trial enrolled 298 pts (TTFields after SRS vs SRS): median age 63 vs 64 years; KPS =80 81% vs 91%; median time from NSCLC diagnosis 1.5 vs 2.2 months; adenocarcinoma 75% vs 79%. Median duration of TTFields therapy was 15.7 (0.1–193.1) weeks; median monthly usage was 67.1% (0.8–96.7%). Time to first intracranial progression from SRS was significantly delayed with TTFields therapy (HR 0.72, 95% CI 0.53–0.98; 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). In the 118 pts receiving immune checkpoint inhibitors (ICI) for their primary disease, TTIP benefit was more pronounced (HR 0.63, 95% CI 0.39–1.0; Cox p=0.049; Fine-Gray test p=0.055; post-hoc). While no difference in TTDP was observed overall (HR 0.76, 95% CI 0.51-1.12, p=0.165; post-hoc), in pts receiving ICI, TTFields therapy delayed TTDP compared with SRS alone (HR 0.41, 95% CI 0.21–0.81; p=0.009; post-hoc). Time to neurocognitive failure, OS and radiological response rate did not differ significantly. 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 global health status, physical functioning and fatigue were observed (post-hoc).Conclusion:
By significantly prolonging time to intracranial progression, without deteriorating QoL or cognitive function, TTFields therapy after SRS is a potential new treatment option for pts with NSCLC BM. .