| Abstrakt: |
Objective: The standard treatment for advanced endometrial cancer (EC) includes platinum-based combination chemotherapy (CT), regardless of the histology, molecular status and the patient's profile. However, EC patients are a particularly frail group of patients, often with co-morbidities. Tolerance of CT can be difficult and induce long-term toxicities. In advanced EC disease, anti-PD1 immunotherapy has shown impressive results amongst mismatch repair deficient (MMRd)/high microsatellite instability (MSI-H) tumors. However, the benefit of adding CT to anti-PD1 is still an opened question. The aim of DOMENICA is to address the question if PD-1 alone has superior efficacy to CT, so that therapy in 1L advanced/recurrent MMRd/MSI-H EC could be de-escalated to avoid CT related toxicities. Methods: DOMENICA is an academic international randomized open-label, phase III trial evaluating the efficacy and safety of dostarlimab versus carboplatin-paclitaxel in patients with MMR deficient (MMRd/MSI-H) relapse or advanced / metastatic EC. Inclusion criteria for the study comprised patients with histologically confirmed EC exhibiting recurrent or advanced disease, including primary stage IIIA to C2 or Stage IV disease, or experiencing their first recurrence of EC without curative treatment, provided they had evaluable disease according to RECIST 1.1 criteria. Additionally, patients with MMRd/MSI-H tumors, determined by institutional MMR immunohistochemistry testing, and those with a performance status (ECOG) of 0-1 were eligible. The primary endpoint is progression-free survival according to RECIST 1.1, assessed by the BICR (Blinded Independent Central Review). Secondary endpoints include overall survival as key secondary endpoint, progression-free survival 2, patients reported outcome, best objective response rate, disease control rate, duration of response rate, safety and tolerability, time to first or second subsequent treatment (TFST, TSST), pharmacokinetics and immunogenicity of dostarlimab. Exploratory objectives include predictive biomarkers, efficacy according to geriatric status. The Study is ongoing in France (GINECO), Spain (GEICO), Italy (MaNGO, MITO), Canada (PMC), Singapore (GCIG), South Korea (KGOG), Japan (GOTIC), Turkey (TRSGO), and UK (NRCI). [ABSTRACT FROM AUTHOR] |
