RARE DISEASE
Chordoma
Chordoma
Chordoma
Synonyms: Notochordal sarcoma
Synonyms: Notochordal sarcoma
Synonyms: Notochordal sarcoma
Drug discovery
3
drugs
With orphan designations
Overview
Chordoma is a rare malignant tumor arising from notochord remnants, typically occurring in the skull base, spine, or sacrum. It is locally aggressive, often recurs despite treatment, and can metastasize. Diagnosis involves imaging and histopathology, with management requiring multidisciplinary care. Current research focuses on molecular targets (e.g., brachyury) and immunotherapy [1][3][9][18].
Burden
Five-year survival: 50–65% (improves to 65–70% with complete resection) [14][16].
High recurrence (~50%) and metastasis rates (30–40%), often impacting neurologic function and quality of life [4][16][19].
Requires long-term surveillance and multidisciplinary care due to chronic morbidity [4][9][19].
Therapies
Surgery: En bloc resection with negative margins is preferred, though challenging due to proximity to critical structures [8][13].
Radiation: High-dose proton beam or carbon ion therapy improves local control post-surgery [13][14].
Systemic therapy: Tyrosine kinase inhibitors (e.g., imatinib, erlotinib) for advanced/metastatic disease; clinical trials exploring brachyury-targeted vaccines [3][18].
Categories: rare bone diseases, rare endocrine diseases, rare genetic diseases, rare neoplastic diseases
Research Papers
1,988 drug discovery papers related to Chordoma, with 4 first-in-class and 7 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,988 drug discovery papers related to Chordoma, with 4 first-in-class and 7 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-03 | An institutional review of clinical outcomes for skull base chordoma: an analysis of 269 cases over 19 years.
The aim of the present study was to review the surgical outcomes of endoscopic skull base surgery (ESBS) for the treatment of skull base chordoma (SBC) at the authors' institution over the past 2 decades. The electronic medical records of patients who underwent resection of primary SBC at the University of Pittsburgh Medical Center from 2001 to 2020 were retrospectively reviewed. Patients were split into two groups: primary or recurrent tumor. The primary outcome in this analysis was extent of resection. Secondary outcomes included progression-free survival (PFS) and complications. This analysis included 194 individual patients on whom 269 total resections were performed. Within the authors' sample, 95 resections were for primary tumors and 174 resections were for recurrent tumors. The mean PFS among tumor patients who received gross-total resection (GTR) was 103.5 months, near-total resection (NTR) was 27.1 months, and subtotal resection (STR) was 12.2 months. Not accounting for adjuvant radiation, GTR allowed for significantly longer PFS than NTR (p < 0.001) or STR (p < 0.001). For tumors that did not receive adjuvant radiation, GTR allowed for significantly longer PFS than non-GTR (p = 0.013). The factors that were associated with GTR were prior radiation (OR 0.302) and institutional experience (OR 1.225). The percentage of GTRs among all tumors in our sample increased significantly and incrementally from 2001 to 2020 (7.7% to 78%, p < 0.001). GTR is an important factor influencing PFS in patients with SBC. Experience with ESBS has a significant effect on outcomes. GTR rates (especially for recurrent tumors) and incidence of complications have improved at the authors' institution, which may be correlated to institutional experience.
2026-06-25 | Targeted Therapy in Recurrent Clival Chordoma: A Case Report of Response to Ivosidenib.
Genetic and molecular alterations in cancer cells can serve as therapeutic targets and enable more precise, individualized treatment strategies. In rare tumors with limited systemic treatment options, molecular profiling may help identify therapeutic opportunities when conventional approaches are exhausted. We report the case of a 72-year-old woman with a long-standing, multiply recurrent clival chordoma and no remaining surgical or radiation options who experienced a meaningful clinical and metabolic response to targeted therapy. Comprehensive tumor molecular profiling identified an activating isocitrate dehydrogenase 1 (IDH1) p. R132C mutation, which guided off-label treatment with the IDH1 inhibitor ivosidenib. Treatment was well tolerated and associated with durable radiographic response with tumor reduction, partial metabolic response on FDG-PET imaging, and clinically significant improvement in neurological symptoms and quality of life. This case highlights the value of molecular tumor board-guided interpretation of genomic alterations and illustrates the potential role of IDH-targeted therapy in select patients with recurrent chordoma.
2026-06-17 | A pooled analysis of phase 2 clinical trials in advanced chordoma.
Chordoma is an ultra-rare malignancy with no approved therapies. In this study, we analyzed individual patient-level data (IPD) for patients with chordoma reconstructed from previously completed clinical trials. Our primary objectives were to synthesize the historical objective response rate (ORR) and to generate a pooled Kaplan-Meier progression-free survival (PFS) curve. Our overarching goal is that these data will inform future trial design and interpretation of results. A literature review was conducted to identify prospective chordoma systemic therapy clinical trials. Eligible studies were required to be prospective; to include locally advanced/metastatic conventional chordoma; to report a PFS Kaplan-Meier curve; and to assess PFS/ORR by RECIST (1.0/1.1). IPD were reconstructed from the PFS curves and data were synthesized to estimate the pooled PFS and ORR. Twelve studies met eligibility, contributing 328 patients (320 response evaluable). The combined ORR was 4.7% and median PFS was 10.8 months (95% CI 9, 12). Sensitivity analyses revealed no significant differences in PFS between studies partitioned by study-level variables. In "leave-one-out" analyses of each study alone versus pooled data, only everolimus/imatinib showed a significantly longer PFS (p = 0.0014), with a median PFS of 14.0 months (95% CI 11.5, NA) compared to 10.0 months (95% CI 8.3,11.2) for the remaining pooled cohort (estimated hazard ratio: 0.50 [95% CI 0.33, 0.77]). IPD from 12 trials were reconstructed and analyzed, consolidating outcomes for 328 trial-eligible patients with chordoma. The estimated overall response rate (ORR) is 4.7% and median PFS 10.8 months, providing a historical benchmark useful for future trial design. Notably, everolimus/imatinib was the only study treatment associated with a statistically significant improvement in PFS, which may warrant further investigation.
2026-07-03 | An institutional review of clinical outcomes for skull base chordoma: an analysis of 269 cases over 19 years.
The aim of the present study was to review the surgical outcomes of endoscopic skull base surgery (ESBS) for the treatment of skull base chordoma (SBC) at the authors' institution over the past 2 decades. The electronic medical records of patients who underwent resection of primary SBC at the University of Pittsburgh Medical Center from 2001 to 2020 were retrospectively reviewed. Patients were split into two groups: primary or recurrent tumor. The primary outcome in this analysis was extent of resection. Secondary outcomes included progression-free survival (PFS) and complications. This analysis included 194 individual patients on whom 269 total resections were performed. Within the authors' sample, 95 resections were for primary tumors and 174 resections were for recurrent tumors. The mean PFS among tumor patients who received gross-total resection (GTR) was 103.5 months, near-total resection (NTR) was 27.1 months, and subtotal resection (STR) was 12.2 months. Not accounting for adjuvant radiation, GTR allowed for significantly longer PFS than NTR (p < 0.001) or STR (p < 0.001). For tumors that did not receive adjuvant radiation, GTR allowed for significantly longer PFS than non-GTR (p = 0.013). The factors that were associated with GTR were prior radiation (OR 0.302) and institutional experience (OR 1.225). The percentage of GTRs among all tumors in our sample increased significantly and incrementally from 2001 to 2020 (7.7% to 78%, p < 0.001). GTR is an important factor influencing PFS in patients with SBC. Experience with ESBS has a significant effect on outcomes. GTR rates (especially for recurrent tumors) and incidence of complications have improved at the authors' institution, which may be correlated to institutional experience.
2026-06-25 | Targeted Therapy in Recurrent Clival Chordoma: A Case Report of Response to Ivosidenib.
Genetic and molecular alterations in cancer cells can serve as therapeutic targets and enable more precise, individualized treatment strategies. In rare tumors with limited systemic treatment options, molecular profiling may help identify therapeutic opportunities when conventional approaches are exhausted. We report the case of a 72-year-old woman with a long-standing, multiply recurrent clival chordoma and no remaining surgical or radiation options who experienced a meaningful clinical and metabolic response to targeted therapy. Comprehensive tumor molecular profiling identified an activating isocitrate dehydrogenase 1 (IDH1) p. R132C mutation, which guided off-label treatment with the IDH1 inhibitor ivosidenib. Treatment was well tolerated and associated with durable radiographic response with tumor reduction, partial metabolic response on FDG-PET imaging, and clinically significant improvement in neurological symptoms and quality of life. This case highlights the value of molecular tumor board-guided interpretation of genomic alterations and illustrates the potential role of IDH-targeted therapy in select patients with recurrent chordoma.
2026-06-17 | A pooled analysis of phase 2 clinical trials in advanced chordoma.
Chordoma is an ultra-rare malignancy with no approved therapies. In this study, we analyzed individual patient-level data (IPD) for patients with chordoma reconstructed from previously completed clinical trials. Our primary objectives were to synthesize the historical objective response rate (ORR) and to generate a pooled Kaplan-Meier progression-free survival (PFS) curve. Our overarching goal is that these data will inform future trial design and interpretation of results. A literature review was conducted to identify prospective chordoma systemic therapy clinical trials. Eligible studies were required to be prospective; to include locally advanced/metastatic conventional chordoma; to report a PFS Kaplan-Meier curve; and to assess PFS/ORR by RECIST (1.0/1.1). IPD were reconstructed from the PFS curves and data were synthesized to estimate the pooled PFS and ORR. Twelve studies met eligibility, contributing 328 patients (320 response evaluable). The combined ORR was 4.7% and median PFS was 10.8 months (95% CI 9, 12). Sensitivity analyses revealed no significant differences in PFS between studies partitioned by study-level variables. In "leave-one-out" analyses of each study alone versus pooled data, only everolimus/imatinib showed a significantly longer PFS (p = 0.0014), with a median PFS of 14.0 months (95% CI 11.5, NA) compared to 10.0 months (95% CI 8.3,11.2) for the remaining pooled cohort (estimated hazard ratio: 0.50 [95% CI 0.33, 0.77]). IPD from 12 trials were reconstructed and analyzed, consolidating outcomes for 328 trial-eligible patients with chordoma. The estimated overall response rate (ORR) is 4.7% and median PFS 10.8 months, providing a historical benchmark useful for future trial design. Notably, everolimus/imatinib was the only study treatment associated with a statistically significant improvement in PFS, which may warrant further investigation.
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Drug Discovery Landscape
3 orphan drug designations for Chordoma.
3 orphan drug designations for Chordoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
afatanib and palbociclib | small molecules | FDA | 2020-11-12 | — | Collaborations Pharmaceuticals, Inc |
tazemetostat | small molecules | FDA | 2018-05-23 | — | Epizyme, Inc. |
BN-Brachyury; a heterologous prime/boost therapeutic cancer vaccine composed of MVA-BN-Brachyury (prime) and FPV-Brachyury (boost) | vaccines | FDA | 2018-04-30 | — | Bavarian Nordic A/S |
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