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; Eyub Y Akdemir; Tugce Kutuk; Can Ilgin; Manmeet S Ahluwalia; Wenya L Bi; Jaishri Blakeley; Karan S Dixit; Ian F Dunn; Evanthia Galanis; Norbert Galldiks; Raymond Y Huang; Derek R Johnson; Thomas J Kaley; David O Kamson; Sylvia C Kurz; Michael W McDermott; Yazmin Odia; Matthias Preusser; Jeffrey Raizer; David A Reardon; C Leland Rogers; Roberta Ruda; David Schiff; Michael A Vogelbaum; Michael Weller; Patrick Y Wen; Minesh P Mehta

doi:10.1093/neuonc/noaf009

Benchmarking the Efficacy of Salvage Systemic Therapies for Recurrent Meningioma: A RANO Group Systematic Review and Meta-analysis to Guide Clinical Trial Design

Neuro Oncol. 2025 Jan 14:noaf009. doi: 10.1093/neuonc/noaf009. Online ahead of print.

Authors

Rupesh Kotecha¹, Eyub Y Akdemir^{1

2}, Tugce Kutuk¹, Can Ilgin³, Manmeet S Ahluwalia⁴, Wenya L Bi⁵, Jaishri Blakeley⁶, Karan S Dixit⁷, Ian F Dunn⁸, Evanthia Galanis⁹, Norbert Galldiks¹⁰, Raymond Y Huang¹¹, Derek R Johnson¹², Thomas J Kaley¹³, David O Kamson¹⁴, Sylvia C Kurz¹⁵, Michael W McDermott¹⁶, Yazmin Odia¹⁷, Matthias Preusser¹⁸, Jeffrey Raizer⁷, David A Reardon¹⁹, C Leland Rogers²⁰, Roberta Ruda²¹, David Schiff²², Michael A Vogelbaum²³, Michael Weller²⁴, Patrick Y Wen²⁵, Minesh P Mehta¹

Affiliations

¹ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
² Department of Radiation Oncology, Koç University School of Medicine, Istanbul, Turkey.
³ Department of Radiation Oncology, Institute of Oncology, University of Istanbul, Istanbul, Turkey.
⁴ Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
⁵ Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Division of Neuro-Oncology, Department of Neurology, Feinberg School of Medicine Northwestern University, Chicago, IL, USA.
⁸ Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
⁹ Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.
¹⁰ Department of Neurology, Faculty of Medicine, University of Cologne and University Hospital Cologne, Cologne, Germany; Research Center Juelich, Institute of Neuroscience and Medicine, Juelich, Germany.
¹¹ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹² Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA; Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹³ Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁴ Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁵ Department of Neuro-Oncology, Yale University School of Medicine, New Haven, CT, USA.
¹⁶ Department of Neurosurgery, Miami Neuroscience Institute, Baptist Health South Florida, Miami, FL, USA.
¹⁷ Department of Neuro-Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
¹⁸ Division of Oncology, Department of Medicine, Medical University of Vienna, Vienna, Austria.
¹⁹ Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, USA; Harvard Medical School, Boston, USA.
²⁰ Department of Radiation Oncology, GammaWest Cancer Services, Salt Lake City, UT, USA.
²¹ Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Turin, Italy.
²² Division of Neuro-Oncology, Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
²³ Department of NeuroOncology, Moffitt Cancer Center, Tampa, FL, USA.
²⁴ Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
²⁵ Center for Neuro-Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, Massachusetts, USA.

PMID: 39807850
DOI: 10.1093/neuonc/noaf009

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 RANO 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 I-squared 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 grade 2-3 meningiomas, the PFS-6 was 38.0% (95% CI: 28.3-48.8%, I2=68%). In 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 grade 2-3 tumors, the PFS-6 rate with targeted therapy and immunotherapy was 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 grade 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.

Keywords: clinical trials; meningioma; recurrent; refractory; systemic therapy.

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