Leiomyosarcomas (LMS) represent 10-15% of soft tissue and visceral sarcomas, most frequently uterine. LMS are moderately chemosensitive. Options in 2nd-line therapy after anthracycline-based chemotherapy for metastatic/advanced disease include Gemcitabine (G), trabectedin and pazopanib (P) monotherapy. Currently no combination therapy is better than monochemotherapy. LMS03 is an open-label multicentre single-group phase II study designed to assess the efficacy and tolerance of G+P in this 2nd-line setting.
Patients (pts) aged ≥18 years, ECOG ≤2 with metastatic or relapsed LMS (uterine or soft tissue) after 1st-line anthracycline chemotherapy failure were eligible. Pts were treated with G 1,000 mg/m2 on days 1 and 8 of each 21 day cycle (maximum 8 cycles), in combination with oral daily P (800 mg/day), until disease progression/unacceptable toxicity. Tumour response was assessed every 6 weeks (RECIST) with 9-month PFS rate as primary endpoint. Inacceptable and promising 9-month PFS rates were defined, in Intention-To-Treat (ITT), as 32% (Median PFS=5.5 months (mo)) and 44% (Median PFS=7.5 mo). Secondary objectives included control rate (CR/PR/SD), overall survival, toxicity.
From 2011 to 2016, 18 French centres included 106 pts: mean age of 59.8 years, mainly women (85.8%), ECOG 0 (63.5%), and uterine LMS (61%). Pts were treated with P+G for a median of 3.8 mo; 40 pts (38%) completed the 8 cycles of combination. Pts were treated with P for a median of 4.2 mo. The 9-mo PFS was 32.1% (CI 95% 23.2-41.4; n = 105, ITT) and 34.6% (CI 95% 24.9-44.4; n = 95, per-protocol). Median PFS was 6.5 mo (CI 95% 5.6-8.2; n = 105, ITT) and 7.1 mo (CI 95% 5.7-8.3; n = 95, per-protocol). The 12-week control rate was 83.6% (11 PR and 45 SD; 67 pts evaluable). Grade 3-4 AE (>30%) with P+G were: neutropenia (76 [72.4%]), leucopenia (59 [56.2%]) and thrombocytopenia (40 [38.1%]).
The study results are negative in ITT with median PFS < 7.5 mo but nearly positive when considering per protocol results. In term of safety the combination P+G could be well managed, without unexpected toxicity.
Clinical trial identification
Legal entity responsible for the study
N. Isambert: Congress participations supported by PharmaMar, AZ, Roche, Novartis, Celgene. Board: Lilly. All other authors have declared no conflicts of interest.