(P 215) IMPACT OF FRONTLINE SYSTEMIC TREATMENT CHOICE ON CLINICAL OUTCOME IN ADVANCED LEIOMYOSARCOMA: A MULTI-CENTRE RETROSPECTIVE CANSARCC STUDY

Objective: Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma (STS) subtype with the uterus as the most common anatomical site of origin. Commonly used frontline chemotherapy regimens for advanced STS are doxorubicin- or gemcitabine-based, with doxorubicin monotherapy widely regarded as standard. Combination chemotherapy with gemcitabine and docetaxel remains a popular choice over doxorubicin despite data from the randomized phase 3 GeDDIS trial that demonstrated no difference in survival between the 2 regimens. In this multi-centre, retrospective study, we aimed to evaluate whether the choice of frontline treatment influences clinical outcome in advanced LMS patients in a real-world setting.

Methods: Advanced LMS patients (uterine and non-uterine) who received frontline systemic treatment with doxorubicin- or gemcitabine-based chemotherapy at 4 Canadian sarcoma centres between 2010 and 2022 were included. Data were extracted from the curated and ethics board-approved Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database. The primary and secondary endpoints were overall survival (OS) by choice of frontline treatment regimen and by the sequence of systemic treatments in the front and second lines, respectively. Survival analyses were performed using Kaplan-Meier method and differences in time-to-event endpoints between patient groups were assessed using the log-rank test, with p < 0.05 considered significant.

Results: A total of 217 patients (median age 58 years, range 28 – 92 years) were included (summarized on Table 1), among whom 102 (47%) had primary uterine LMS (uLMS). Median follow up was 15.4 months (range 0.4 – 84.1 months). Frontline systemic treatment was doxorubicin monotherapy in 61 patients (28%) and gemcitabine + docetaxel in 83 patients (38%) with median OS of 19.2 and 14.8 months, respectively (p = 0.21). Median OS was 17.8 months in patients who received frontline doxorubicin-based (n = 103) versus 16.1 months with gemcitabine-based (n=114) treatment (p = 0.17). In the uLMS subgroup, median OS was 15.2 versus 12.3 months with frontline doxorubicin-based (n = 43) and gemcitabine-based (n = 59) treatments, respectively (p = 0.23), while non-uLMS patients treated with frontline doxorubicin-based (n = 55) and gemcitabine-based (n = 55) treatments had median OS of 25.2 and 21.5 months, respectively (p = 0.72). Regarding sequence of treatments, patients who received frontline doxorubicin monotherapy followed by second-line gemcitabine + docetaxel (n = 18) had median OS of 22.0 versus 18.2 months among those patients (n = 18) who were treated with the reverse sequence (p = 0.06).

Conclusion: OS was numerically longer with frontline doxorubicin compared with gemcitabine + docetaxel in all LMS, but the difference was not statistically significant, in keeping with clinical trial data. Frontline doxorubicin followed by gemcitabine + docetaxel did not lead to longer survival than the reverse sequence. There was no difference in overall survival between patients who received frontline doxorubicin-based treatment compared to those who received gemcitabine-based treatment, regardless of primary LMS location. Differences in toxicity, quality of life, and cost of treatment delivery between regimens should therefore be considered in the choice of frontline treatment for advanced LMS patients.