LMS-02: A phase II single-arm multicenter study of doxorubicin in combination with trabectedin as a first-line treatment of advanced uterine leiomyosarcoma (u-LMS) and soft tissue LMS (ST-LMS): First results in patients with u-LMS.

Abstract

10505 Background: U-LMS and ST-LMS are rare tumours with poor prognosis when metastatic or locally advanced, presenting moderate chemosensitivity mainly to doxorubicine (doxo), ifosfamide (ifo), cisplatin, gemcitabine (gem) and trabectidine (trab). Response rates (RR) in combination therapies (1stline) does not exceed 50% for U-LMS and 35% for ST-LMS. The most active ones are doxo combinations (most of the time with ifo or dacarbazine) and gem + docetaxel (in particular in U-LMS) with a mean response durations of 3 to 6 months. Trab was demonstrated a definite activity on pre-treated LMS (RR of approximately 20% in LMS overall [U-LMS in particular]). In view of these encouraging results on LMS, a study combining trab with doxo as first line therapy for LMS is of interest. Methods: Patients (pts) received every 3 weeks, 6 cycles of doxo 60 mg/m2 followed by trab 1.1 mg/m23-h at day 1, and pegfilgrastim 6 mg on Day 2. Study primary objective: to determine the disease control rate (DCR) (ORR+SD). Secondary objectives: PFS 12 wks, RR by RECIST and duration, OS and toxicities. Patients were stratified into U-LMS (n=45) and ST-LMS (n=62) group. Herein, we report the first results in pts with U-LMS; mature data will be shown in ASCO Meeting. Results: 45 pts with U-LMS have been enrolled until November 2012. Median age is 58 years, 38 where of with data collected for at least 1 cycle, 85% had metastatic disease (mostly lung 30/33, liver and bone), and 26 pts have received 6 cycles. For 33 pts with at least 1 disease assessment (every 2 cycles), the ORR was 55% (18 PR) and 13 SD (39%) had SD disease for a DCR of 94% at that time. Presently, the median PFS at 12 weeks is 94,3% [95%IC:86-100]. Main grade 3-4 toxicities in 187 cycles were neutropenia (51%), febrile neutropenia (7%), thrombopenia (14%), anemia (7%), fatigue (5%), vomiting (6%) and transiet transaminase increase (22%). Conclusions: The combination of trab plus doxo seems to be an effective first-line treatment for pts with U-LMS, with meaningful clinical benefits and an acceptable and manageable safety profile. Clinical trial information: 2009-012430-70.