Retrospective analysis of BRCA-altered uterine sarcoma treated with poly(ADP-ribose) polymerase inhibitors Journal Article
| Authors: | Rao, M.; Merrill, M.; Troxel, M.; Chiang, S.; Momeni-Boroujeni, A.; Hensley, M. L.; Schram, A. M. |
| Article Title: | Retrospective analysis of BRCA-altered uterine sarcoma treated with poly(ADP-ribose) polymerase inhibitors |
| Abstract: | PURPOSEUterine sarcomas are rare, aggressive tumors with limited chemotherapy responsiveness. Poly(ADP-ribose) polymerase inhibitors (PARPis) have emerged as targeted therapies for patients with BRCA mutations across multiple cancer types, with anecdotal responses in uterine sarcoma. This retrospective, single-center study aims to describe relevant genomic and clinical features of patients with BRCA-altered uterine sarcoma and the efficacy of PARPis in this population.METHODSEligible patients included all histopathologically confirmed uterine sarcoma with pathogenic BRCA alterations identified through Memorial Sloan Kettering Cancer Center-integrated mutation profiling of actionable cancer targets, excluding carcinosarcoma. Genomic, pathologic, and treatment information was extracted from the cBioPortal database and chart review.RESULTSThirty-five patients were identified with uterine sarcoma harboring pathogenic BRCA alterations, including 33 BRCA2 alterations (70% homozygous deletions, 3% structural variants, 27% mutations) and two BRCA1 mutations. Leiomyosarcoma (LMS) was the most common histology (86%). Thirteen patients with uterine LMS were treated with PARPis in the recurrent/metastatic therapy setting (54% combination therapy regimens) with an overall response rate (ORR) of 46% (1 of 6 for PARPi monotherapy, 5 of 7 for PARPi combination regimens), a clinical benefit rate (CBR) of 62%, and a median progression-free survival (PFS) of 13.2 months (range, 1.0-71.9). The median PFS ratio compared with previous systemic therapy was 1.9 (range, 0.4-53.9), and 58% had a PFS ratio of >= 1.3. The median time on PARPi was 14.5 months (range, 1.3-71.9). The ORR for patients with somatic BRCA2 deletions was 60% (n = 6 of 10), with a CBR of 80% (n = 8 of 10). One patient with metastatic disease and progression on previous hormonal and chemotherapy demonstrated a complete response to PARP/PD-L1 inhibitor combination therapy, ongoing for 70+ months.CONCLUSIONPARPis demonstrate promising efficacy in patients with uterine LMS with somatic BRCA2 deletions. |
| Keywords: | chemotherapy; tumors; trabectedin; leiomyosarcoma; trial; soft-tissue sarcoma; 1st-line treatment; gemcitabine plus docetaxel; randomized phase-ii; spanish group |
| Journal Title: | JCO Precision Oncology |
| Volume: | 9 |
| ISSN: | 2473-4284 |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-04-01 |
| Start Page: | e2400765 |
| Language: | English |
| ACCESSION: | WOS:001449406200001 |
| DOI: | 10.1200/po-24-00765 |
| PROVIDER: | wos |
| PMCID: | PMC11949232 |
| PUBMED: | 40117531 |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Alison M. Schram -- Source: Wos |
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