Systemic therapy for advanced epithelioid sarcoma: A meta-analysis of effectiveness and safety study.

Abstract

e23558 Background: Epithelioid sarcoma (ES) is a rare and aggressive type of soft tissue sarcoma (STS) with limited evidence available on systemic therapies. Due to the rarity of the disease, high-level evidence for guiding systemic therapy is minimal, and treatment approaches are often based on data from broader studies on STS. This meta-analysis examines the efficacy and safety of chemotherapy, targeted therapy, and immunotherapy in the management of ES. Methods: This meta-analysis adhered to PRISMA guidelines. A systematic review of PubMed, Embase, and Cochrane Library was conducted to identify studies reporting systemic therapy outcomes in ES with a search cutoff until December 2024. Data on overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed and documented. Keywords included "epithelioid sarcoma," "systemic therapy," "chemotherapy," "targeted therapy," and "immunotherapy." Results: Twenty-two studies involving 340 ES patients were included. Doxorubicin-based regimens (gemcitabine, ifosfamide) showed an ORR of 10–20%, median PFS of 3–6 months, and median OS of 9–12 months. Combination regimens improved ORR (20–30%) but with increased toxicity. Grade 3/4 toxicities in 45% of patients, primarily hematologic (neutropenia, anemia). Tazemetostat (EZH2 inhibitor) demonstrated an ORR of approximately 15%, disease control rate of approximately 40%, median PFS of 5.5 months, and OS of 12–14 months in patients with SMARCB1/INI1 loss, with minimal grade 3–4 AEs (fatigue and nausea). Immunotherapy (anti-PD-1/PD-L1) yielded ORRs of approximately 15%, with durable responses in select patients with PDL1 > 1%. Data on Pazopainb is limited with one study reporting PFS of 5.5 months without any documented OS. Conclusions: The results highlight the limited efficacy of conventional chemotherapy in epithelioid sarcoma, with modest response rates and survival outcomes. Targeted therapies, such as tazemetostat, offer a promising alternative for patients with specific molecular profiles. Immune checkpoint inhibitors are emerging as effective options, particularly in PD-L1-positive cases, underscoring the need for biomarker-driven treatment strategies. mTOR and EGFR inhibiting treatment are under investigation and other combination strategies are under investigation. Despite these advances, challenges remain, including resistance mechanisms, limited durable responses in unselected populations, and the lack of large randomized trials. Future research should focus on novel combination strategies and further exploration of biomarkers to refine patient selection.