Regorafenib as maintenance therapy after first-line doxorubicin-based chemotherapy in advanced non-adipocytic soft tissue sarcomas patients: a double-blind randomised trial
Mené en France sur 126 patients atteints d'un sarcome des tissus mous de stade avancé (âge médian : 58 ans), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité du régorafénib en traitement d'entretien avec une chimiothérapie de première ligne à base de doxorubicine
Background: There is no approved maintenance therapy in advanced non-adipocytic soft tissue sarcomas (NASTS). 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 2 trial assessing the activity and safety of regorafenib (120 mg/d, 3 weeks / 4) in patients with NASTS, who had stable disease or partial response after 6 cycles of doxorubicin-based chemotherapy as first line treatment for advanced disease. The primary endpoint was progression-free survival (PFS) according to RECIST 1.1 evaluated by blinded central review (BCR). Based on the following assumptions: PFS (placebo)=4 months, expected PFS (regorafenib)=7 months, Hazard Ratio HR=0.57, 1-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 Nov 2022. Female patients accounted for 55% of total enrolment. The median age was 58 years (range, 18-85). The most common histological subtype was leiomyosarcoma (59%). The primary objective was assessable in 122 patients (109 events). Median PFS by BCR 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 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 NASTS. This was associated with a non-significant trend of overall survival improvement.
Annals of Oncology , résumé 2024