INTERNATIONAL JOURNAL OF CANCER, cilt.2025, sa.1, ss.1-10, 2025 (SCI-Expanded, Scopus)
Abstract Nonuterine leiomyosarcoma (NU-LMS) is a rare and biologically distinct subtype of soft tissue sarcoma (STS) with clinical behavior differing from that of uterine leiomyosarcoma. In advanced or metastatic STS, immunotherapy has demonstrated only modest activity, and chemotherapy remains the cornerstone of treatment. However, there is a persistent unmet need for more effective and better-tolerated options in this population. This multicenter, retrospective study included 150 patients with histologically confirmed metastatic NU-LMS who received first-line doxorubicin–ifosfamide (AI) or gemcitabine–docetaxel (GD) at 26 oncology centers in Turkey between 2010 and 2024. The primary endpoint was overall survival (OS). Survival was analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Of 150 patients, 79 received AI and 71 received GD. Median OS for the entire cohort was 21.0 months. Median OS was 22.0 months with AI and 19.1 months with GD (p = .18), median progression-free survival was 7.3 versus 6.1 months (p = .66), and overall response rate was 25.3% versus 29.6% (p = .58), indicating no statistically significant differences in efficacy between the two regimens. Hematologic toxicities were less frequent with GD. AI and GD demonstrated comparable efficacy as firstline regimens for advanced or metastatic NU-LMS, with fewer hematologic toxicities observed for GD. Tumor location may have prognostic implications. These findings support individualized treatment selection and highlight the need for prospective studies in this rare and understudied sarcoma subtype, while the recent LMS-04 trial underscores the importance of future comparisons with doxorubicin–trabectedin to further refine first-line strategies in LMS. KEYWORDS doxorubicin–ifosfamide, gemcitabine–docetaxel, metastatic soft tissue sarcoma, nonuterine leiomyosarcoma, real-world study What's New? Current treatment regimens for advanced nonuterine leiomyosarcoma (NU-LMS) include singleagent doxorubicin, gemcitabine–docetaxel (GD), and anthracycline-based combinations, such as doxorubicin–ifosfamide (AI) or doxorubicin–trabectedin. However, limited data are available on the efficacy and tolerance of these various options. Here, first-line AI was compared to GD in patients with metastatic NU-LMS who underwent treatment in Turkey between 2010 and 2024. Treatment efficacy did not differ between the two regimens, while GD was associated with fewer hematologic toxicities. Treatment outcomes were influenced by tumor location. Future comparisons of AI and GD against other regimens are needed to help further optimize treatment approaches for metastatic NU-LMS.