1731TiP - EREMISS: Efficacy of regorafenib (REG) as maintenance therapy in non-adipocytic soft tissue sarcomas (STS) having received 1st-line doxorubicin-based chemotherapy (Doxo-CT)

Abstract

BackgroundIn advanced STS, median progression-free survival (PFS) remains at 4 months (mo) and median overall survival (OS) is about 12-18mo after Doxo-CT. There is currently no maintenance therapy available. A phase III trial has shown a modest benefit of a maintenance with ridafolimus compared to placebo (PBO) (PFS, 17.7 vs 14.6 weeks, HR=0.72). REG is an orally bioavailable multikinase inhibitor with meaningful activity in doxorubicin-refractory non-adipocytic STS. In a prior randomized phase II trial (REGOSARC; NCT01900743), median PFS was 4.0mo with REG compared to 1.0 with PBO (HR=0.36, p<0.0001) and median OS was 13.4 vs 9.0mo (HR=0.67; p=0.059). Trial designEREMISS (NCT03793361) is a multicenter (17 centers from the French Sarcoma Group) double-blind controlled randomized phase II trial assessing efficacy and safety of REG compared to PBO as maintenance therapy in metastatic / locally advanced STS experiencing stable disease (SD) or partial response (PR) after 6 cycles of Doxo-CT as 1st-line. The primary endpoint is PFS (RECIST 1.1, centrally reviewed). Secondary endpoints are efficacy (OS, Objective response, time to start subsequent therapy), safety and benefit/risk ratio (Q-TWIST). The randomization is balanced 1:1 and controlled for histology (leiomyosarcoma/synovial sarcoma/other sarcoma), response to CT (SD/PR) and centers. Pts receive either REG (120mg/d 21/28 days) or PBO until unacceptable toxicity, progression or consent withdrawal. There is no cross-over in this trial. Main eligibility criteria are: age ≥18; histologically-proven non-adipocytic STS, metastatic / locally advanced STS not amenable to curative intent surgery, PS<2, measurable disease, SD or PR after 6 cycles of Doxo-CT. Based on the following assumptions: PFS, 7 (REG) vs 4mo (PBO), HR=0.57, 1-sided α=5% and β=10%, the required number of events is 110 and the sample size is 126 pts. The planned study duration is 30 months. Enrolment is open since 12/2018. Clinical trial identificationNCT03793361. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureA. Le Cesne: Honoraria (self): PharmaMar; Honoraria (self): Lilly; Honoraria (self): Novartis. All other authors have declared no conflicts of interest.