Abstract 7352: Gemcitabine-docetaxol-cisplatin and everolimus in advanced soft tissue sarcomas: Clinical outcomes and prognostic biomarkers

Abstract Background: Soft tissue sarcomas (STSs) are rare mesenchymal tumors with poor prognosis. While anthracycline-based regimens remain first-line treatment, subsequent options are limited. This study evaluated a novel combination regimen of gemcitabine, docetaxel, cisplatin with everolimus (G-GTC/E), which combines conventional cytotoxic agents with targeted therapy. Methods: A retrospective analysis was conducted between June 2009 and September 2024 on STS patients treated with G-GTC/E at our institution. The regimen was administered every three weeks: Day 1 - gemcitabine 800 mg/m2 and everolimus 10 mg; Day 8 - gemcitabine 60 mg/m2, cisplatin 60 mg/m2, docetaxel 60 mg/m2, and everolimus 10 mg; Day 15 - everolimus 10 mg. We analyzed baseline characteristics, inflammatory markers, and treatment outcomes. Statistical analyses included Kaplan-Meier survival estimates and Cox proportional hazards models for prognostic factors. Results: Among 74 enrolled patients with advanced STSs, the ORR was 46% (CR 2.7%, PR 43.2%) with a DCR of 68.9%. The mOS was 16.2 months (95% CI: 10.9-21.4) and mPFS was 5.9 months (95% CI: 3.3-8.5). Histological subtypes included LMS (32.4%), UPS (18.9%), angiosarcoma (6.8%), synovial sarcoma (6.8%), LPS (5.4%), MPNST (5.4%), and others (24.3%). Survival varied significantly across subtypes, with synovial sarcoma showing the most favorable mOS at 29.8 months (95% CI: 0-76.3), followed by LMS at 21.7 months (95% CI: 9.6-33.9), while UPS showed the poorest survival of 8.6 months (95% CI: 0-20.8). Primary sites included extremities (40.5%), abdominal/thoracic visceral organs (29.7%), retroperitoneum (13.5%), trunk (10.8%), and head and neck (5.4%). Head/neck sarcomas had the longest mOS at 27.4 months (95% CI: 12.2-42.6), followed by retroperitoneal (24.8 months; 95% CI: 16.5-33.0) and visceral sarcomas (23.6 months; 95% CI: 14.0-33.3). For prognostic factors, elevated CRP, neutrophil-lymphocyte-ratio, platelet-lymphocyte-ratio, and systemic inflammatory index predicted poor OS. Monocyte-lymphocyte-ratio showed similar trend without significance (p=0.119). All inflammatory markers suggested inferior PFS without statistical significance. Low albumin levels predicted poor outcomes in both OS and PFS. Grade 4 hematological toxicities included neutropeniq (40%), thrombocytopenia (35%), and anemia (10%). Grade 3/4 diarrhea and skin rashes occurred in 16.2% and 25% of patients, respectively. Conclusion: G-GTC/E demonstrated promising efficacy as a second-line treatment for advanced STS. Careful monitoring for thrombocytopenia, diarrhea and skin reactions is essential. Elevated inflammatory markers and low albumin levels predicted poor outcomes, suggesting their potential utility in patient stratification for G-GTC/E therapy in advanced STS. Citation Format: Wen-Chi Wu, Chueh-Chuan Yen. Gemcitabine-docetaxol-cisplatin and everolimus in advanced soft tissue sarcomas: Clinical outcomes and prognostic biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7352.