The combination of durvalumab and platinum-based chemotherapy, followed by maintenance therapy with either durvalumab plus olaparib or durvalumab alone, elicited a statistically significant and clinically meaningful improvement in progression-free survival in patients with newly diagnosed, advanced or recurrent endometrial cancer.
The combination of durvalumab (Imfinzi) and platinum-based chemotherapy, followed by maintenance therapy with either durvalumab plus olaparib (Lynparza) or durvalumab alone, elicited a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs standard-of-care chemotherapy alone in patients with newly diagnosed, advanced or recurrent endometrial cancer, according to data from the phase 3 DUO-E trial (NCT04269200).1
Although overall survival (OS) data were immature at the time of this analysis, a favorable trend was observed for both durvalumab-based regimens. Full data will be presented at an upcoming medical meeting and shared with 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. These combinations could provide physicians with new treatment approaches to improve outcomes for patients,” Shannon N. Westin, MD, professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center in Houston, and principal investigator of the DUO-E trial, stated in a news release.
DUO-E was a 3-arm, randomized, double-blind, placebo-controlled multicenter trial that enrolled 699 patients at least 18 years of age with histologically confirmed, newly diagnosed or recurrent stage III/IV epithelial endometrial carcinoma. Patients with all histologies, including carcinosarcomas, were permitted to enroll, although those with sarcomas were excluded.2
Patients also needed to be naïve to first-line systemic therapy. In those with recurrent disease, prior systemic therapy was only allowed if given in the adjuvant setting at least 12 months prior to study enrollment. Other key inclusion criteria included a tumor sample available for mismatch repair (MMR) evaluation and an ECOG performance status of 0 or 1.
Those who had a history of leptomeningeal carcinomatosis, brain metastases or spinal cord compression, prior treatment with PARP inhibitors, or any prior exposure to immune-mediated therapy were excluded from the trial.
Patients were randomly assigned to receive 1120 mg of durvalumab or placebo once every 3 weeks in combination with standard-of-care chemotherapy consisting of carboplatin and paclitaxel. Following the completion of chemotherapy, patients received 1500 mg of durvalumab or placebo once every 4 weeks as maintenance, either in combination with 300 mg of olaparib twice per day or placebo, for 24 months or until progressive disease.1
MMR status served as one of the stratification factors.
PFS for the 2 durvalumab arms vs the chemotherapy alone arm served as the primary end point. Secondary end points included OS, objective response rate (ORR), duration of response, time to second progression, time to first subsequent treatment, time to second subsequent treatment, and safety.2
Safety findings for durvalumab plus chemotherapy and durvalumab plus olaparib were consistent with the toxicity profiles of the agents observed in prior clinical trials.1
“These DUO-E data demonstrate for the first time the power of combining immunotherapy and a PARP inhibitor to provide meaningful clinical improvements for patients with endometrial cancer,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said. “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.”