Oluwaseun O Akinduro1, Paola Suarez-Meade1, Diogo Garcia1, Desmond A Brown2, Rachel Sarabia-Estrada1, Steven Attia3, Ziya L Gokaslan4, Alfredo Quiñones-Hinojosa5. 1. Brain Tumor Stem Cell Laboratory, Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd. S, Jacksonville, FL, 32224, USA. 2. Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA. 3. Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA. 4. Department of Neurosurgery, Warren Alpert Medical School of Brown University, Providence, RI, USA. 5. Brain Tumor Stem Cell Laboratory, Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd. S, Jacksonville, FL, 32224, USA. quinones@mayo.edu.
Abstract
BACKGROUND: Chordoma is a rare but devastating tumor that arises in the cranial skull base or spine. There are currently no US Food and Drug Administration-approved targeted therapies for chordoma, and little understanding of whether using more than one therapy has benefit over monotherapy. OBJECTIVE: The objective of this study was to systematically review the current status of clinical trials completed for patients with chordoma to determine if multimodal therapy offers a benefit in progression-free survival over monomodal therapy. METHODS: We performed a systematic review of the literature according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to review the available clinical trials of targeted therapy for chordoma. We compiled the clinical data to determine if there is a benefit of multimodal therapy over monotherapy. RESULTS: Our search resulted in 11 clinical trials including 270 patients with advanced chordoma who were treated with targeted therapies. The most commonly employed targeted therapies acted within the following pathways: platelet-derived growth factor receptor (187 patients), vascular endothelial growth factor (66 patients), and mammalian target of rapamycin (43 patients). Reported progression-free survival for included studies ranged from 2.5 to 58 months, with the longest progression-free survival in a trial that included a platelet-derived growth factor receptor inhibitor, nilotinib, and concurrent radiotherapy (58.2 months). There was a higher range of progression-free survival for trials treating patients with multimodal therapy (10.2-14 months vs 2.5-9.2 months, except for a monotherapy trial published in 2020 with a progression-free survival of 18 months), and those published in 2018 or later (14-58.2 months vs 2.5-10.2 months). Only 23% of patients with chordoma in published clinical trials have been treated with multimodal therapy. CONCLUSIONS: Progression-free survival may be enhanced by the use of targeted therapy with concurrent radiotherapy, use of multimodal therapy, and use of newer targeted therapy. Future clinical trials should consider use of concurrent radiotherapy and multimodal therapy for patients with advanced chordoma.
BACKGROUND: Chordoma is a rare but devastating tumor that arises in the cranial skull base or spine. There are currently no US Food and Drug Administration-approved targeted therapies for chordoma, and little understanding of whether using more than one therapy has benefit over monotherapy. OBJECTIVE: The objective of this study was to systematically review the current status of clinical trials completed for patients with chordoma to determine if multimodal therapy offers a benefit in progression-free survival over monomodal therapy. METHODS: We performed a systematic review of the literature according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to review the available clinical trials of targeted therapy for chordoma. We compiled the clinical data to determine if there is a benefit of multimodal therapy over monotherapy. RESULTS: Our search resulted in 11 clinical trials including 270 patients with advanced chordoma who were treated with targeted therapies. The most commonly employed targeted therapies acted within the following pathways: platelet-derived growth factor receptor (187 patients), vascular endothelial growth factor (66 patients), and mammalian target of rapamycin (43 patients). Reported progression-free survival for included studies ranged from 2.5 to 58 months, with the longest progression-free survival in a trial that included a platelet-derived growth factor receptor inhibitor, nilotinib, and concurrent radiotherapy (58.2 months). There was a higher range of progression-free survival for trials treating patients with multimodal therapy (10.2-14 months vs 2.5-9.2 months, except for a monotherapy trial published in 2020 with a progression-free survival of 18 months), and those published in 2018 or later (14-58.2 months vs 2.5-10.2 months). Only 23% of patients with chordoma in published clinical trials have been treated with multimodal therapy. CONCLUSIONS: Progression-free survival may be enhanced by the use of targeted therapy with concurrent radiotherapy, use of multimodal therapy, and use of newer targeted therapy. Future clinical trials should consider use of concurrent radiotherapy and multimodal therapy for patients with advanced chordoma.
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