Benchmarking the efficacy of salvage systemic therapies for recurrent meningioma: A RANO group systematic review and meta-analysis to guide clinical trial design
Rupesh Kotecha, Eyüb Yaşar Akdemir, Tuğçe Kütük, Can Ilgın, Manmeet S. Ahluwalia, Wenya Linda Bi, Jaishri O. Blakeley, Karan Dixit, Ian F. Dunn, Evanthia Galanis, Norbert Galldiks, Raymond Y. Huang, Derek R. Johnson, Thomas Kaley, David Kamson, Sylvia C. Kurz, Michael McDermott, Yazmín Odia, Matthias Preusser, Jeffrey Raizer, David A. Reardon, Leland Rogers, Roberta Rudà, David Schiff, Michael A. Vogelbaum, Michael Weller, Patrick Y. Wen, Minesh P. Mehta
Abstract
BACKGROUND: Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propose a "rate of probable interest" to inform future clinical trial design and development on behalf of the Response Assessment in Neuro-Oncology meningioma group. METHODS: PubMed, ClinicalTrials.gov, and ASCOpubs databases were screened for clinical trials evaluating the activity of systemic therapies for adults with recurrent meningiomas. The pooled progression-free survival at 6-months and 1-year (PFS-6 and PFS-1 year) values were calculated using the random effects technique with I2 indices. RESULTS: The pooled PFS-6 and PFS-1 year rates for recurrent WHO grade 1 meningiomas were 43.6% (95% CI: 22.7-67.0%, I2 = 80%) and 21.7% (95% CI: 6.2-53.9%, I2 = 76%), and for grades 2-3 meningiomas, the PFS-6 was 38.0% (95% CI: 28.3-48.8%, I2 = 68%). In the targeted therapy group, PFS-6 and PFS-1 year rates stood at 62.0% (I2 = 58%) and 49.0% (I2 = 63%) for grade 1, while for grades 2-3 tumors, the PFS-6 rates with targeted therapy and immunotherapy were 42.1% (I² = 60%) and 46.0% (I² = 0%), respectively. The benchmarks were set at 67% and 54% for PFS-6 and PFS-1 year for grade 1 tumors, and PFS-6 of 49% for grades 2-3 tumors. CONCLUSIONS: Several studies have reported outcomes in patients with recurrent meningiomas testing a variety of agents with modest, but variable and progressively increasing activity. In this context, we recommend new benchmarks for future trials to define efficacy of future investigational therapies.