(P 461) A RETROSPECTIVE ANALYSIS OF PATIENTS WITH CONVENTIONAL CHORDOMA TREATED WITH SYSTEMIC THERAPY

Objective: Chordoma (CH) is a rare tumor arising along the axial skeleton, with ~ 350 cases per year in the U.S. Despite standard treatments, many patients experience locoregional relapse or metastasis with limited salvage options. No FDA-approved systemic therapies exist for metastatic or recurrent CH. This study investigates real-world systemic treatment patterns and associated outcomes in conventional CH.

Methods: A retrospective analysis was performed on patients treated for conventional chordoma, excluding those with poorly-differentiated or de-differentiated histology. Progression-free survival (PFS) was calculated for different systemic agents and lines of treatment. Progression was defined as primary tumor enlargement or new metastatic lesions.

Results: From December 1986 to March 2025, 202 patients were identified in our electronic medical record as receiving systemic therapy; 173 had conventional chordoma and were included in this analysis. The median age at diagnosis was 47 years (range, 1-87), with 80 (46%) females and 93 (54%) males. Ten patients had metastatic disease at diagnosis. Primary tumor locations included the base of skull (n=77), mobile spine (n=41), and sacrum (n=55). Surgical resection included gross total resection (GTR)/near total resection (NTR) (n=48), subtotal resection (STR) (n=98), and biopsy only (n=27). 162 patients received adjuvant radiotherapy, with a median total dose of 76 Gy (range, 30-88.4 Gy). 150 out of 173 had local recurrences or developed metastases. Sixty-nine of these patients were treated with tyrosine kinase inhibitors (TKI), immunotherapy, CDK4/6 inhibitors, and pemetrexed outside of clinical trials. Of these patients, we observed a median PFS of 6.5 months with first-line treatment (n=69), 6.0 months with second-line treatment (n=27), and 5.2 months with third-line treatment (n=18). Specific median PFS by agent class (any line of therapy) were: imatinib alone or combination (n=59, 6.3 months), epidermal growth factor receptor inhibitors (EGFRi) (n=17, 7.6 months), immunotherapy (n=16, 9.2 months), CDK4/6 inhibitors (n=11, 8.5 months), and pemetrexed (n=8, 7.3 months). At last follow-up, 111 patients had died from progressive CH, 10 from other causes, and 52 were alive.

Conclusion: This analysis provides valuable insights into historical and current systemic therapy patterns in conventional chordoma. The data underscore the need for further research and clinical trials to identify more effective systemic strategies for this rare disease.