Real-world evidence of tazemetostat in epithelioid sarcoma patients.

Abstract

e23539 Background: Epithelioid sarcoma (ES) is an ultra-rare and aggressive mesenchymal soft tissue sarcoma (STS) with limited therapeutic options. Therapies targeting EZH2 have shown promise, with tazemetostat being the first FDA-approved treatment for this histology. Tazemetostat was approved in Hainan (Boao Lecheng International Medical Tourism Pilot Zone) in May 2022, but has not received approval for the rest of mainland China. Several ES patients (pts) have been treatment with tazemetostat in Hainan. Here we present a retrospective analysis of ES pts treated with tazemetostat-based regimens at Ruijin Hainan Hospital, and this analysis was the first report on tazemetostat in Chinese ES pts. Methods: We retrospectively reviewed all pts with histologically confirmed ES treated with tazemetostat-based regimens at Ruijin Hainan Hospital between 2022 and 2025. Patient demographics, disease characteristics, treatment regimens, and clinical outcomes were collected. Endpoints included real-world progression-free survival (rwPFS), overall survival (OS), and safety. Results: Nineteen advanced ES pts with loss of SMARCB1/INI1 received tazemetostat-based regimens. The median age was 35 years (Range: 16-69), with 68.42% female pts. The two clinical subsets comprise 9 patients of the distal type and 10 patients of the proximal type. Patients received a median of 2 lines of previous therapies (range 1-5), with 8 pts (42.11%) receiving tazemetostat-based regimens as a first-line treatment. Most pts (n=13) had previously received chemotherapy (most anthracycline, n=12), anti-angiogenic targeted therapy (n=10), and immune checkpoint inhibitors (n=3). 14 pts received tazemetostat monotherapy, and 5 pts received tazemetostat combined with immunotherapy. As of August 30, 2025, with a median follow-up of 15.51mo (range: 1.08-24.44), median rwPFS was 10.55mo (95% CI: 7.62-NE) with 12-mo and 18-mo PFS of 41% (95% CI: 15-100%) and 20% (95% CI: 4-100%). Median OS was 17.18mo (95% CI: 4.24-NE) with 12-mo and 24-mo OS of 52% (95% CI: 32-84%) and 26% (95%CI: 9%-77%).In different subsets, the PFS was 17.22mo for distal-type and 7.62mo for proximal-type. Median PFS was 13.33mo in treatment-naïve pts and 10.55mo in previously treated pts. Favorable PFS was observed in combination regimens compared with tazemetostat monotherapy (7.62 vs 13.89mo). Compared with pts who received anti-angiogenic targeted therapy in prior therapy, pts without showed longer PFS (10.55mo vs 13.36mo, p=0.11). Treatment-emergent adverse events (TEAEs) were mostly mild (grade 1-2), the most common were hemorrhage (21%), vomiting (21%), decreased white blood cell count (16%), AST increased (16%), decreased lymphocyte count (16%), and anemia (16%). Grade 3-4 TEAEs were recorded in 1 pt with decreased platelet count. Conclusions: The median rwPFS of 10.55 months demonstrated the efficacy of tazemetostat in advanced ES patients. Updated data will be presented in the future.