Evaluation of the efficacy of systemic therapy for advanced uterine leiomyosarcoma: A systematic review, meta-analysis, and meta-regression analysis

Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta-analysis and meta-regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta-analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta-regression analysis was performed to estimate the association between the study-specific hazard ratios and specific demographic variables. A meta-analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First-line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44-0.52) and second-line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39-0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67-0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63-0.75) showed the greatest benefits when used as first-line and second-line chemotherapies, respectively. Subgroup meta-analysis results revealed that dual-regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III-IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p < 0.001). Our findings provide a basis for designing new therapeutic strategies and can potentially guide clinical practice toward better prognoses for uLMS patients with advanced, metastatic, and relapsing disease.