Durvalumab combinations boost PFS in advanced endometrial cancer

medwireNews: The addition of durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib significantly improves the progression-free survival (PFS) of women with advanced endometrial cancer, findings indicate. “DUO-E is the first phase 3 study to demonstrate that durvalumab and olaparib confers a PFS benefit and provides new treatment options for patients with advanced and recurrent endometrial cancer,” said presenter Shannon Westin (University of Texas MD Anderson Cancer Center, Houston, USA) at the ESMO Congress 2023 in Madrid, Spain. Outlining the rationale for the trial, she explained that recent research has shown that “immunotherapy in combination with chemotherapy has activity in endometrial cancer, particularly in mismatch repair-deficient disease,” and “[a]dding a PARP inhibitor may improve outcomes.” The researchers enrolled 718 patients with newly diagnosed advanced (FIGO stage III or IV) or recurrent endometrial cancer and randomly assigned them to one of three trial arms: durvalumab 1120 mg every 3 weeks alongside carboplatin plus paclitaxel for six cycles, followed by maintenance durvalumab 1500 mg every 4 weeks in those without disease progression (n=238); durvalumab 1120 mg every 3 weeks alongside carboplatin plus paclitaxel for six cycles, followed by maintenance durvalumab 1500 mg every 4 weeks plus olaparib 300 mg twice daily in those without disease progression (n=239); placebo alongside carboplatin plus paclitaxel for six cycles, followed by maintenance placebo in those without disease progression (n=241). At a median follow-up of 12.6–15.4 months, PFS was significantly improved with the use of the PD-L1 inhibitor, at a median 10.2 and 15.1 months in the durvalumab and durvalumab plus olaparib arms, respectively, versus 9.6 months in the control arm. This equated to hazard ratios (HRs) for progression or death of 0.71 and 0.55, respectively. A prespecified exploratory analysis of PFS by MMR status showed a similar magnitude of benefit with durvalumab and durvalumab plus olaparib among the 20% of patients with MMR deficient disease (HRs=0.42 and 0.41, respectively). Patients with MMR proficient disease also benefited from use of the PD-L1 inhibitor (HR=0.77), but the magnitude was greater when the maintenance regimen also included olaparib (HR=0.57). Another subgroup analysis by PD-L1 status showed a significant improvement in PFS in the durvalumab and durvalumab plus olaparib groups among those with PD-L1-positive (69% of patients) but not PD-L1-negative (31%) tumors. “Interim analysis of overall survival [OS] in the intent-to-treat population was not statistically significant at this time, with limited 28% data maturity,” said Westin. “However, the Kaplan–Meier curve showed a trend towards improvement for both experimental arms” and “updated OS analyses with longer follow-up are planned and will be reported after the second preplanned interim analysis.” With regard to the overall safety profile during the chemotherapy and maintenance phases, grade 3 or worse adverse events (AEs) occurred in a higher proportion of women in the durvalumab–olaparib arm than the durvalumab or control arm, at 67.2% versus 54.9% and 56.4%, respectively. And this was also the case for the proportion with dose interruptions or delays of study treatment due to AEs (68.9 vs 54.5 and 50.0%, respectively). However, the rates of AE-related treatment discontinuation were similar across the durvalumab, durvalumab–olaparib, and control groups, at 20.9%, 24.4%, and 18.6%, respectively. Domenica Lorusso (Fondazione Policlinico Universitario “A Gemelli” IRCCS, Rome, Italy), who discussed the presentation, said that “the main limitation of the trial, unfortunately, is that the trial was not powered to have a formal comparison between the two experiment arms.” She continued: “So what is the added benefit of olaparib to durvalumab remains an unanswered question.” The DUO-E results were simultaneously published in the Journal of Clinical Oncology. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group ESMO Congress 2023; Madrid, Spain: 20–24 October J Clin Oncol 2023; doi:10.1200/JCO.23.02132

ERS Congress 2024

Springer Medicine

Durvalumab combinations boost PFS in advanced endometrial cancer

Related topics

ERS Congress 2024

Springer Medicine

Please log in to get access to this content

Related topics