AstraZeneca Announces Positive Phase III DUO-E Trial Results for Imfinzi-Based Regimen in First-Line Advanced or Recurrent Endometrial Cancer

On May 26, AstraZeneca announced high-level positive results from the Phase III DUO-E study. In newly diagnosed advanced or recurrent endometrial cancer patients, compared with standard chemotherapy, Imfinzi (durvalumab) combined with platinum-based chemotherapy, followed by maintenance therapy with Imfinzi + Lynparza (olaparib) or Imfinzi monotherapy, demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS). Imfinzi combined with Lynparza as maintenance therapy showed greater clinical benefit.

DUO-E Study (GOG 3041/ENGOT-EN10) is a three-arm, randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial. A total of 699 patients with newly diagnosed or recurrent stage III or IV epithelial endometrial cancer (excluding sarcoma) were randomly assigned to receive either 1120mg of Imfinzi or placebo once every 3 weeks in combination with standard platinum-based chemotherapy. After discontinuation of chemotherapy, patients received maintenance therapy with 1500mg of Imfinzi or placebo once every 4 weeks, or in combination with 300mg BID of Lynparza or placebo until disease progression for up to 24 months.

The dual primary endpoints of the trial were PFS in the Imfinzi + placebo group vs. placebo group and PFS in the Imfinzi + olaparib group vs. placebo group, with mismatch repair (MMR) status as one of the stratification factors. Key secondary endpoints included OS, objective response rate (ORR), duration of response (DoR), as well as safety and tolerability. The trial was conducted across 253 study sites in 22 countries, including the United States, Europe, South America, and Asia.

At the time of this analysis, the overall survival (OS) data were not yet mature; however, both treatment regimens showed a favorable trend of benefit.

The safety and tolerability of Imfinzi in combination with chemotherapy and Imfinzi in combination with Lynparza were generally consistent with what was observed in previous clinical trials and the known profiles of the individual drugs. AstraZeneca stated that it will present these data at an upcoming medical conference and engage in discussions with regulatory authorities.

Endometrial cancer is the sixth most common cancer in women globally, with over 417,000 cases diagnosed and more than 97,000 deaths in 2020. It is projected that the number of diagnoses will increase by nearly 40% by 2040. The majority of patients with endometrial cancer are diagnosed when the cancer has not yet metastasized, at which point it can typically be treated with surgery and/or radiation therapy, resulting in a high 5-year survival rate (approximately 95%). However, patients with advanced-stage disease (stages III-IV) usually undergo chemotherapy, and their prognosis is poor, with a 5-year survival rate dropping to around 20-30%.

In the indication for first-line treatment of advanced or recurrent endometrial cancer, AstraZeneca faces competition from Merck and GSK.

On March 27 this year, Merck announced the PFS results of the Phase III NRG-GY018 study of PD-1 monoclonal antibody Pembrolizumab (Keytruda) combined with standard chemotherapy (carboplatin and paclitaxel) for the treatment of patients with stage III-IV or recurrent endometrial cancer. Compared with chemotherapy alone, Pembrolizumab combined with chemotherapy significantly reduced the risk of disease progression or death by 46% in pMMR patients (HR=0.54, 95%CI: 0.41-0.71, P<0.00001); and significantly reduced the risk of disease progression or death by 70% in dMMR patients (HR=0.30, 95%CI: 0.19-0.48, P<0.00001).

On the same day, GSK announced the Phase III RUBY study data on dostarlimab, a PD-1 monoclonal antibody, for first-line treatment of endometrial cancer. The results showed that the extension of PFS was statistically significant and clinically meaningful. GSK stated that based on the positive data from this study, it would submit an application for marketing approval of dostarlimab as a first-line treatment for endometrial cancer in the first half of 2023.

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