Impact of Frontline Systemic Treatment Choice on Clinical Outcome in Advanced Leiomyosarcoma: A CanSaRCC Study

Frontline systemic treatment selection for advanced leiomyosarcoma (LMS) remains variable in routine practice. Gemcitabine-based regimens are frequently used despite randomized evidence of non-superiority compared with doxorubicin-based regimens and greater complexity in treatment delivery.

This multi-centre retrospective cohort study included advanced/metastatic LMS patients treated with frontline doxorubicin- or gemcitabine-based chemotherapy at four Canadian sarcoma centres (2010-2022). The primary endpoint was overall survival (OS). Secondary endpoints were time to second-line treatment (T2T) and number of subsequent systemic treatment lines. Subgroup analyses were conducted by primary tumor site (uterine vs. non-uterine LMS).

Among 217 patients, median OS was 17.1 months (95% CI 14.8-21.1). OS did not differ between frontline doxorubicin- and gemcitabine-based regimens (17.8 vs. 16.1 months; p = 0.16), nor did T2T (5.8 vs. 6.3 months; p = 0.77). Non-uterine primary site and surgery following frontline systemic treatment were independently associated with improved OS. Median OS was longer for non-uterine versus uterine LMS (23 vs. 12.8 months; p < 0.001).

In this large real-world LMS cohort, outcomes were not influenced by frontline chemotherapy choice. These findings support prioritizing toxicity, quality of life, cost, and treatment delivery burden when selecting frontline therapy, particularly where doxorubicin/trabectedin use is limited.