PMID- 36181606 OWN - NLM STAT- MEDLINE DCOM- 20230308 LR - 20230309 IS - 1573-7373 (Electronic) IS - 0167-594X (Print) IS - 0167-594X (Linking) VI - 161 IP - 2 DP - 2023 Jan TI - Emerging systemic treatment options in meningioma. PG - 245-258 LID - 10.1007/s11060-022-04148-8 [doi] AB - PURPOSE: Meningiomas are the most frequently diagnosed intracranial neoplasms. Usually, they are treated by surgical resection in curative intent. Radiotherapy and stereotactic radiosurgery are commonly applied in the adjuvant setting in newly diagnosed atypical (CNS WHO grade 2), and anaplastic (CNS WHO grade 3) meningioma, especially if gross total resection is not feasible, and in recurrent cases. Conversely, the evidence for pharmacotherapy in meningioma is scarce. METHODS: The available literature of systemic treatment in meningioma was screened using PubMed, and ongoing clinical trials were explored using ClinicalTrials.gov. RESULTS: Classical cytotoxic agents, somatostatin analogs, and antihormone treatments have shown only limited efficacy. In contrast, tyrosine kinase inhibitors and monoclonal antibodies, especially those targeting angiogenic signaling such as sunitinib and bevacizumab, have shown promising antitumoral activity in small phase 2 trials. Moreover, results of recent landmark studies on (epi-)genetic alterations in meningioma revealed potential therapeutic targets which are currently under investigation. These include inhibitors of mammalian target of rapamycin (mTOR), focal adhesion kinase (FAK), cyclin-dependent kinases (CDK), phosphoinositide-3-kinase (PI3K), sonic hedgehog signaling, and histone deacetylases. In addition, clinical trials evaluating immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab and avelumab are currently being conducted and early results suggest clinically meaningful responses in a subset of patients. CONCLUSIONS: There is a paucity of high-level evidence on systemic treatment options in meningioma. However, interesting novel treatment targets have been identified in the last decade. Positive signals of anti-angiogenic agents, genomically targeted agents and immunotherapy in early phase trials should be confirmed in large prospective controlled trials. CI - (c) 2022. The Author(s). FAU - Mair, Maximilian J AU - Mair MJ AD - Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. AD - Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria. FAU - Berghoff, Anna S AU - Berghoff AS AD - Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. AD - Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria. FAU - Brastianos, Priscilla K AU - Brastianos PK AD - Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. AD - Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Preusser, Matthias AU - Preusser M AD - Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. matthias.preusser@meduniwien.ac.at. AD - Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria. matthias.preusser@meduniwien.ac.at. LA - eng PT - Journal Article PT - Review DEP - 20221001 PL - United States TA - J Neurooncol JT - Journal of neuro-oncology JID - 8309335 RN - 0 (Hedgehog Proteins) RN - 0 (Antineoplastic Agents) SB - IM MH - Humans MH - *Meningioma/drug therapy/radiotherapy MH - *Meningeal Neoplasms/drug therapy/radiotherapy MH - Prospective Studies MH - Hedgehog Proteins MH - *Antineoplastic Agents/therapeutic use PMC - PMC9989003 OTO - NOTNLM OT - Chemotherapy OT - Immunotherapy OT - Meningioma OT - Systemic treatment OT - Targeted therapy COIS- Maximilian J. Mair has received travel support from Pierre Fabre. Anna Sophie Berghoff has received research support from Daiichi Sankyo, Roche, and honoraria for lectures, consultation or advisory board participation from Roche, Bristol-Meyers Squibb, Merck, Daiichi Sankyo as well as travel support from Roche, Amgen and AbbVie. Priscilla Brastianos has consulted for Angiochem, Genentech-Roche, Lilly, Tesaro, ElevateBio, Axiom Healthcare Strategies, Pfizer (Array), Dantari, SK Life Sciences, Advise Connect Inspire (ICI), Voyager Therapeutics and Sintetica, and has received grant/research support to MGH from Merck, BMS, Mirati, Kinnate and Lilli and honoraria from Merck, Genentech-Roche, Pfizer and Lilly. The following for-profit companies have supported clinical trials conducted by PKB with payments made to the institution: Merck, Pfizer, Lilly, Bristol-Myers Squibb, AstraZeneca, and Genentech-Roche. Matthias Preusser has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen. The following for-profit companies have supported clinical trials and contracted research conducted by MP with payments made to his institution: Boehringer-Ingelheim, Bristol-Myers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dome, Novocure, GlaxoSmithKline, AbbVie. EDAT- 2022/10/02 06:00 MHDA- 2023/03/09 06:00 PMCR- 2022/10/01 CRDT- 2022/10/01 11:16 PHST- 2022/07/22 00:00 [received] PHST- 2022/09/25 00:00 [accepted] PHST- 2022/10/02 06:00 [pubmed] PHST- 2023/03/09 06:00 [medline] PHST- 2022/10/01 11:16 [entrez] PHST- 2022/10/01 00:00 [pmc-release] AID - 10.1007/s11060-022-04148-8 [pii] AID - 4148 [pii] AID - 10.1007/s11060-022-04148-8 [doi] PST - ppublish SO - J Neurooncol. 2023 Jan;161(2):245-258. doi: 10.1007/s11060-022-04148-8. Epub 2022 Oct 1.