(P 155) BRCA2-MUTATED CONVENTIONAL CHONDROSARCOMA RESPONDING TO PARP INHIBITION: A CASE REPORT

Objective: Chondrosarcomas commonly harbor recurrent mutations in IDH1/2, as well as alterations such as CDKN2A and COL2A1 inactivation, while homologous recombination deficiency is rare. Here, we describe the case of a young adult diagnosed with a high-grade conventional chondrosarcoma harboring a somatic BRCA2 pathogenic variant and highlight the observed radiological response to PARP inhibition.

Methods: We describe the clinical course of a 22-year-old female diagnosed in January 2021 with grade 3 chondrosarcoma of the proximal tibia. Following surgical resection and adjuvant surveillance, pulmonary metastases developed five months postoperatively. She received multiple lines of systemic therapy, including anthracycline-based chemotherapy and pazopanib. Tumor genomic profiling revealed a pathogenic somatic BRCA2 alteration (p.Trp1692Metfs*32; allele frequency: 95.7%). Based on this finding, treatment with the PARP inhibitor olaparib was initiated as fourth-line therapy in July 2024.

Results: Despite prior disease progression on three lines of systemic therapy, olaparib led to a partial radiological response per RECIST criteria, with up to a 50% reduction in pulmonary lesions at the first disease assessment, 2 months after treatment initiation. Interruptions due to grade 3 hepatitis, pneumonitis, and neutropenia required temporary dose reduction. However, the patient was able to resume the original dose without further adverse events and maintained prolonged disease stability, with ongoing therapeutic benefit at last follow-up in June 2025.

Conclusion: This case highlights the potential sensitivity of BRCA-mutated conventional chondrosarcomas to PARP inhibition. It reinforces the rationale for tumor-agnostic approaches in molecularly selected sarcoma patients and supports further investigation of homologous recombination deficiency as a therapeutic target in bone sarcomas. Evaluation of the patient’s germline BRCA2 status is ongoing to better characterize the biological context of this response.