Regorafenib as maintenance therapy after first-line doxorubicin-based chemotherapy in advanced non-adipocytic soft tissue sarcomas patients: a double-blind randomised trial

BACKGROUND: There is no approved maintenance therapy in advanced non-adipocytic soft tissue sarcomas (STS). We explore here the role of regorafenib as a potential maintenance therapy after first-line treatment. PATIENTS AND METHODS: EREMISS (NCT03793361) was a double-blind, placebo-controlled, comparative, 1 : 1 randomised phase II trial assessing the activity and safety of regorafenib (120 mg/day, 3 weeks on/1 week off) in patients with non-adipocytic STS, who had stable disease or partial response after six cycles of doxorubicin-based chemotherapy as first-line treatment of advanced disease. The primary endpoint was progression-free survival (PFS) according to RECIST 1.1 evaluated by blinded central review. Based on the following assumptions: PFS (placebo) = 4 months, expected PFS (regorafenib) = 7 months, hazard ratio (HR) = 0.57, one-sided α = 0.05 and β = 0.10, 110 events and 126 patients were required. This study was supported by French National Cancer Institute, a patient advocacy group and Bayer HealthCare. RESULTS: The study population consisted of 126 patients enrolled in 17 centres from May 2019 to November 2022. Female patients accounted for 55% of total enrolment. The median age was 58 years (range 18-85 years). The most common histological subtype was leiomyosarcoma (59%). The primary objective was assessable in 122 patients (109 events). Median PFS by blinded central review was 3.5 (placebo) versus 5.6 months (regorafenib) (HR = 0.53, 95% CI 0.36-0.78; P = 0.001). Median overall survival was 20.5 versus 27.6 months (HR = 0.78, 95% CI 0.50-1.22, P = 0.28). The proportion of patients with grade ≥3 adverse events was 4.8% (placebo) versus 56.3% (regorafenib). The most common grade ≥3 clinical adverse events in the regorafenib arm were asthenia (9%), arterial hypertension (8%), and rash (8%). CONCLUSION: This trial met its primary objective, regorafenib significantly delayed disease progression after first-line treatment in advanced non-adipocytic STS. This was associated with a non-significant trend of overall survival improvement.