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Targeted Therapy for Chordoma: Key Molecular Signaling Pathways and the Role of Multimodal Therapy

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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.

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Authors and Affiliations

  1. Brain Tumor Stem Cell Laboratory, Department of Neurologic Surgery, Mayo Clinic, 4500 San Pablo Rd. S, Jacksonville, FL, 32224, USA

    Oluwaseun O. Akinduro, Paola Suarez-Meade, Diogo Garcia, Rachel Sarabia-Estrada & Alfredo Quiñones-Hinojosa

  2. Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA

    Desmond A. Brown

  3. Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA

    Steven Attia

  4. Department of Neurosurgery, Warren Alpert Medical School of Brown University, Providence, RI, USA

    Ziya L. Gokaslan

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  1. Oluwaseun O. Akinduro
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Correspondence to Alfredo Quiñones-Hinojosa.

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Oluwaseun O. Akinduro, Paola Suarez-Meade, Diogo Garcia, Desmond A. Brown, Rachel Sarabia-Estrada, Steven Attia, Ziya Gokaslan, and Alfredo Quiñones-Hinojosa have no conflicts of interest that are directly relevant to the content of this article.

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OOA wrote the manuscript, provided Fig. 2, conducted the literature search, and approved the finalized manuscript. PS provided Fig. 1 and contributed to the editing of the manuscript. DG conducted the literature search and provided the search strategy. DAB conducted the literature search and edited the manuscript. RS, SA, and ZLG critically revised the manuscript. AQ critically revised the manuscript and supervised the study.

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Akinduro, O.O., Suarez-Meade, P., Garcia, D. et al. Targeted Therapy for Chordoma: Key Molecular Signaling Pathways and the Role of Multimodal Therapy. Targ Oncol 16, 325–337 (2021). https://doi.org/10.1007/s11523-021-00814-5

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