Shannon N. Westin, M.D., M.P.H., F.A.C.O.G. from MD Anderson discusses an ASCO 2020 abstract entitled – DUO-E/GOG-3041/ENGOT-EN10: a randomized phase III trial of first-line carboplatin (carb) and paclitaxel (pac) in combination with durvalumab (durva), followed by maintenance durva with or without olaparib (ola), in patients (pts) with newly diagnosed (nd) advanced or recurrent endometrial cancer (EC)
Context:
Progress in EC care that offers progression-free survival (PFS) and overall survival (OS) benefits is a high unmet need. EC tumors are susceptible (Pectasides et al. Gynecol Oncol 2008) to carb / pac. Poly(ADP-ribose) polymerase inhibitor (PARPi) ola (with or without bevacizumab) maintenance therapy has resulted in substantial PFS benefits in advanced ovarian cancer pts with either nd (SOLO1, Moore et al. NEJM 2018; PAOLA-1, Ray-Coquard et al. NEJM 2019) or recurrent (SOLO2, Pujade-Lauraine et al. Lancet Oncol 2017; Research 19, Friedlander et al. Br J Cancer 2018) platinum-sensitive disease, rega-sensitive disease, rega-sensitive disease, rega-sensitive disease PARPi sensitivity may be predicted by EC molecular features (de Jonge et al. Clin Cancer Res 2019; Auguste et al. Mod Pathol 2018). In preclinical BRCA1 mutant ovarian model PARPi has been shown to prime the immune microenvironment (Higuchi et al. Cancer Immunol Res 2015). The antitumor activity of the anti-programmed cell death ligand-1 (anti-PD-L1) blocker durva (Antill et al. J Clin Oncol 2019) and anti-programmed cell death-1 (anti-PD-1) antibody therapies (Makker et al. ESMO 2019; Oaknin et al. SGO 2019) in EC pts was demonstrated in clinical trials. The DUO-E analysis (EUDRACT 2019-004112-60, D9311C00001, NCT04269200) will investigate whether the addition of durva to carb / pac, accompanied by maintenance treatment with durva (with or without ola), improves PFS in pts with advanced or chronic EC.
Approaches:
Qualified pts must have nd Stage III / IV or recurrent EC for this multicenter, double-blind, Phase III trial and be naive to the first-line chemotherapy. Pts are randomized (1:1:1; n=~233 per arm) to: arm A) carb / pac + placebo (pbo) (q3w for six cycles) followed by pbo maintenance therapy; arm B) carb / pac + durva (1120 mg; q3w for six cycles) followed by durva maintenance therapy (1500 mg q4w) + pbo (bid tablets); or arm C) carb / pac + durva (1120 mg; q3w for six cycles) followed by durva maintenance therapy (1500 mg q4w) + ola (bid tablets); Pts received medication with care before progression of the disease. Primary endpoint: PFS (RECIST 1.1) of arm B vs. arm A measured by an investigator. Main secondary endpoints: arm C vs. arm A; arm B vs. arm A; arm C vs. arm A; and arm C vs A. In Q1 2020, enrollment started. Details on clinical trials: 2019-004112-60.