Positive high-level results from the DUO-E Phase III trial showed Imfinzi (durvalumab) in combination with platinum-based chemotherapy followed by either Imfinzi plus Lynparza (olaparib) or Imfinzi alone as maintenance therapy both demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care chemotherapy alone in patients with newly diagnosed advanced or recurrent endometrial cancer. There was a greater clinical benefit observed with the combination of Imfinzi and Lynparza as maintenance treatment.
Overall survival (OS) data were immature at the time of this analysis however, a favourable trend was observed for both treatment regimens.
Endometrial cancer is the 6th most common cancer in women worldwide, with over 417,000 patients diagnosed and over 97,000 deaths in 2020.1 Diagnoses are expected to rise by almost 40% by 2040.2 The current standard of care for advanced endometrial cancer is chemotherapy.3,4 However, long-term outcomes in 1st-line endometrial cancer remain poor and novel treatment options are needed.5,6
Shannon N. Westin, Professor of Gynaecologic Oncology and Reproductive Medicine at the University of Texas MD Anderson Cancer Center, and principal investigator of the DUO-E trial, said: "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."
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "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. These results underscore our ambition to redefine cancer care and we hope to bring this innovative Imfinzi and Lynparza combination to endometrial cancer patients as soon as possible."
The safety and tolerability profile of Imfinzi plus chemotherapy and of Imfinzi in combination with Lynparza was broadly consistent with that observed in prior clinical trials and the known profiles of the individual medicines.7,8
These data will be presented at a forthcoming medical meeting, and we look forward to discussing them with health authorities.
Notes
Endometrial cancer
Endometrial cancer is a highly heterogenous disease that originates in the tissue lining of the womb and is most common in women who have already been through the menopause, with the average age at diagnosis being over 60 years old.9-11 Both the incidence and mortality of endometrial cancer are expected to increase from 417,400 cases and 97,400 deaths in 2020 to 608,130 cases and 157,813 deaths in 2040.1,2
The majority of patients with endometrial cancer are diagnosed at an early stage of disease where the cancer is confined to the uterus. They are typically treated with surgery and/or radiation and the 5-year survival rate is high (approximately 95%). However, patients with advanced disease (Stage III-IV) are usually treated with chemotherapy and have a much poorer prognosis, with a 5-year survival rate falling to around 20-30%.4,5,11,12,13
For patients where the disease has already advanced or returned, treatment options are limited as the cancer is not considered likely to respond to hormonal therapy and will be treated with chemotherapy.5,6
DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi in combination with platinum-based chemotherapy (carboplatin and paclitaxel) followed by Imfinzi with Lynparza or Imfinzi alone as maintenance therapy versus platinum-based chemotherapy alone as a treatment for patients with newly diagnosed advanced or recurrent endometrial cancer.
The DUO-E trial randomised 699 patients with newly diagnosed or recurrent Stage III or IV epithelial endometrial carcinoma (excluding sarcomas) to receive either 1120mg of Imfinzi or placebo, given every three weeks in combination with standard-of-care platinum-based chemotherapy. Following cessation of chemotherapy, patients were given either 1500mg of Imfinzi or placebo every four weeks as maintenance, either in combination with 300mg BID (2x150mg tablets, twice a day) of Lynparza or placebo until progressive disease for 24 months.
The dual primary endpoint was PFS. Mismatch repair (MMR) status was one of the stratification factors. Key secondary endpoints included OS, objective response rate (ORR), duration of response (DoR) and safety and tolerability. The trial was conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.
