Adjuvant gemcitabine plus docetaxel followed by doxorubicin versus observation for uterus-limited, high-grade leiomyosarcoma: A phase III GOG study.

Abstract

5505 Background: We conducted a phase III trial to determine whether adjuvant chemotherapy with gemcitabine-docetaxel followed by doxorubicin improves survival compared to observation in women with resected, uterus-confined, high grade LMS. Methods: Women with uterus-confined high grade LMS, confirmed disease-free by post-resection imaging, were randomly assigned to treatment with gemcitabine-docetaxel x 4 cycles, followed by doxorubicin x 4 cycles (CHEMO) or to observation (OBS). All were followed by CT or MR imaging every 4 mos for 3 yrs, then every 6 mos for 2 yrs for recurrence. The primary endpoint was overall survival. Results: The study was opened with international collaboration. 38 of the target accrual of 216 patients (pts) were enrolled, after which the study was closed for National Cancer Institute-defined accrual futility. 20 pts were assigned to CHEMO and 18 to OBS. 3 pts assigned to CHEMO never received treatment. Among the 17 pts treated with at least one cycle of CHEMO grade 3 or 4 toxicities were observed in 47%; among 18 pts assigned to OBS, 1 had grade 3 hypertension. There were 6 deaths, (5 - CHEMO, 1-OBS), all due to disease. Over 48 mos, the restricted mean survival time (RMST) for OS in the CHEMO arm was estimated to be 34.3 mos (95% CI: 25.3 mos – 43.3 mos); RMST for OS in the OBS arm was estimated to be 46.4 mos (95% CI: 43.6 mos – 49.1 mos). There were 8 recurrences in each arm. Over 24 mos, the RMST for RFS in the CHEMO arm was estimated to be 18.1 mos (95% CI: 14.2 mos – 22.0 mos) and the RMST for RFS in the OBS arm was estimated to be 14.6 mos (95% CI: 10.3 mos – 19.0 mos). The difference in RMST comparing the CHEMO arm to the OBS arm was estimated as 3.4 mos (95% CI: -2.4 mos – 9.3 mos). Neither survival outcome comparison is considered statistically robust due to the small sample size and low number of events. Conclusions: Despite international collaboration to answer the critical question of the role of adjuvant chemotherapy in early-stage uterine LMS, this study was closed for accrual futility. While sample size and number of events preclude robust statistical comparison, observed OS and RFS data do not suggest superior outcomes for patients treated with adjuvant chemotherapy. Clinical trial information: NCT01533207.