Durvalumab Combo Yields Survival Benefit in Advanced Endometrial Cancer

Durvalumab (Imfinzi) plus chemotherapy followed by maintenance with durvalumab alone or in combination with olaparib (Lynparza) demonstrated statistically significant improvements in progression-free survival (PFS) compared with chemotherapy alone in patients with newly diagnosed recurrent or advanced endometrial cancer, according to a press release on data from the phase 3 DUO-E trial (NCT04269200).¹

"These exciting data demonstrate durvalumab immunotherapy can significantly delay disease progression for patients with endometrial cancer and the addition of the PARP inhibitor olaparib can improve the benefit further," according to an expert from The University of Texas MD Anderson Cancer Center.

Investigators identified greater clinical benefit with durvalumab/olaparib maintenance compared with the other study regimens. Additionally, there was a favorable overall survival (OS) trend for durvalumab with or without olaparib as maintenance, although these data were immature at the time of this analysis. Investigators noted that the safety profile of durvalumab plus chemotherapy and durvalumab plus olaparib was comparable with previous reports for each individual agent.

Investigators of the DUO-E trial plan to present detailed findings at a future medical meeting and discuss results with regulatory health authorities.

“These exciting data demonstrate durvalumab immunotherapy can significantly delay disease progression for patients with endometrial cancer and the addition of the PARP inhibitor olaparib can improve the benefit further,” lead investigator Shannon N. Westin, MD, professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, said in the press release. “These combinations could provide physicians with new treatment approaches to improve outcomes for patients.”

Investigators of the multi-center, double-blind phase 3 DUO-E trial assessed the safety and efficacy of durvalumab plus platinum-based chemotherapy followed by maintenance durvalumab on its own or in combination with olaparib for patients with newly diagnosed recurrent or advanced endometrial cancer.

In addition to chemotherapy plus carboplatin and paclitaxel, patients were randomly assigned 1:1:1 to one of 3 arms. Patients received placebo once every 3 weeks for 6 cycles followed by placebo maintenance, 1120 mg of durvalumab once every 3 weeks followed by 1500 mg of durvalumab maintenance every 4 weeks plus placebo, or durvalumab followed by maintenance with durvalumab plus 300 mg of olaparib twice a day.²

The primary end point of the trial was PFS. Secondary end points included OS, objective response rate, duration of response, time to first subsequent therapy, time to second subsequent therapy, time to discontinuation or death, safety and tolerability, and pharmacokinetics.

Patients 18 years and older with histologically confirmed epithelial endometrial carcinoma and newly diagnosed stage III or IV disease or recurrent disease were eligible for enrollment on the trial. Additional eligibility criteria included being resistant to first-line systemic anti-cancer therapy, having available FFPE tumor samples for mismatch repair status evaluation, and an ECOG performance status of 0 or 1.

Patients who had a history of leptomeningeal carcinomatosis or brain metastases or spinal cord compression were unable to enroll on the study. Patients were also unsuitable for enrollment if they had received prior treatment with PARP inhibitors or any previous exposure to immune-mediated therapy including CTLA-4, PD-1, PD-L1, or PD-L2 antibodies.

“These results underscore our ambition to redefine cancer care and we hope to bring this innovative [durvalumab] and [olaparib] combination to patients [with endometrial cancer] as soon as possible,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, concluded.

References

1. IMFINZI® (durvalumab) plus LYNPARZA® (olaparib) and IMFINZI alone both significantly improved progression-free survival in advanced endometrial cancer when added to chemotherapy. News release. AstraZeneca. May 26, 2023. Accessed May 26, 2023. bit.ly/43vt2vu
2. Westin SN, Moore KN, Nieuwenhuysen EV, et al. 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). J Clin Oncol. 2020;38(suppl):TPS6108. doi:10.1200/JCO.2020.38.15_suppl.TPS6108