Doxorubicin-based chemotherapy vs gemcitabine/docetaxel in uterine leiomyosarcoma (ULMS).

Abstract

11564 Background: ULMS is an aggressive uterine smooth muscle cancer. Surgery is standard for localized/advanced ULMS, and the use of adjuvant chemotherapy is controversial. Treatment may involve combination cytotoxic chemotherapy, typically doxorubicin-based regimens (D) or gemcitabine plus docetaxel (GT), which have poor (20-30%) response rates and high toxicity. Given the lack of randomized trial data, this single-center retrospective study compared D vs GT in the adjuvant and metastatic settings of ULMS. Methods: We included patients with confirmed histologic diagnosis of uterine leiomyosarcoma between 2000 and 2024 treated at MD Anderson Cancer Center with either D or GT. Patients were stratified by localized disease and receipt of adjuvant chemotherapy or metastatic disease and receipt of palliative chemotherapy with D or GT in the first-line setting. The primary objective was to assess recurrence-free survival (RFS) in those with localized tumors and progression-free survival (PFS) in those with metastatic tumors treated with either D or GT. RFS and PFS were defined as the time interval from the start time of first line chemotherapy (D or GT) to the time of recurrence/progression or death, whichever occurred first. Kaplan Meier and log rank tests were used to assess survival outcomes. Cox proportional hazards (PH) modeling evaluated whether either regimen independently predicted survival with adjustment for age, primary tumor size, and mitotic index. Data collection is ongoing, and propensity score matching will be performed. Results: We included 76 patients, including 36 with primary localized ULMS and 40 with advanced ULMS. In patients with localized disease, there was no significant difference in RFS between those treated with D vs GT in univariate (p = 0.17) or multivariate (HR (95% CI) = 1.21 (0.35, 4.15), p = 0.76) analyses. In patients with metastatic disease, GT was associated with inferior PFS than those treated with D (HR (95% CI) = 4.45 (1.38, 14.29), p = 0.01) after adjusting for age and primary tumor size in the multivariate Cox PH model. Conclusions: Treatment with D was associated with improved PFS for metastatic ULMS compared to treatment with GT. No significant difference in RFS was observed between the two regimens for localized disease. However, the study may have limited power to detect differences due to small sample size. Updated data analyses with a larger cohort will be presented at the meeting. Localized ULMS (n = 36) Metastatic ULMS (n = 40) Age of diagnosis (median, years) 51.0 52.3 Primary tumor size (median, cm) 10.1 11.0 Mitotic Index (>10 per 10 HPF) 77.8% (n = 28) 82.5% (n = 33) D GT D GT 16.7% (n = 6) 83.3% (n = 30) 30% (n = 12) 70% (n = 28) RFS/PFS (median, months) 10.8 (7.8, 23.0) 7.2 (4.5, 9.2) HR (95% CI) 1.21 (0.35, 4.15) 4.45 (1.38, 14.29) p-value 0.7612 0.0122 Overall Survival (median, years) 6.6 (2.5, 10.3) 4.6 (3.7, 6.7)