Imfinzi plus Lynparza reduced the risk of disease progression or death by 45% vs. chemotherapy in advanced or recurrent endometrial cancer
Positive results from the primary analysis of the DUO-E Phase III trial showed that Imfinzi (durvalumab) plus platinum-based chemotherapy, followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib), both demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy alone in the overall trial population of patients with newly diagnosed advanced or recurrent endometrial cancer.
These results will be presented today in a proffered paper session at the 2023 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain (Presentation #LBA41) and simultaneously published online intheJournal of Clinical Oncology.
In the overall trial population, results showed that treatment with Imfinzi plus chemotherapy followed by Imfinzi plus Lynparza (Imfinzi plus Lynparza Arm) and treatment with Imfinzi plus chemotherapy followed by Imfinzi monotherapy (Imfinzi Arm) demonstrated a reduction in the risk of disease progression or death, by 45% (hazard ratio [HR] 0.55; 95% confidence interval [CI] 0.43-0.69; p<0.0001) and 29% (HR 0.71; 95% CI 0.57-0.89; p=0.003), respectively, versus chemotherapy alone (Control Arm). Median PFS was 15.1 months in the Imfinzi plus Lynparza Arm and 9.6 months in the Control Arm.
Mismatch repair (MMR) status is a biomarker of interest in endometrial cancer, therefore a prespecified exploratory subgroup analysis by MMR status was conducted in DUO-E. Results from the analysis of mismatch repair proficient (pMMR) patients showed a reduction in the risk of disease progression or death in both the Imfinzi plus Lynparza and the Imfinzi Arms, by 43% (HR 0.57; 95% CI 0.44-0.73) and 23% (HR 0.77; 95% CI 0.60-0.97), respectively, versus the Control Arm. Median PFS was 15 months in the Imfinzi plus Lynparza Arm and 9.7 months in the Control Arm.
Results from the analysis of mismatch repair deficient (dMMR) patients showed a similar reduction in the risk of disease progression or death in both the Imfinzi plus Lynparza and the Imfinzi Arms, by 59% (HR 0.41; 95% CI 0.21-0.75) and 58% (HR 0.42; 95% CI 0.22-0.80), respectively, versus the Control Arm.
Interim overall survival (OS) data showed a favourable trend for both treatment regimens in the overall population.
Shannon N. Westin, Professor of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, and principal investigator of the trial, said, “These findings showcase, for the first time, the potential of combining immunotherapy with a PARP inhibitor to deliver significant clinical improvements for these patients. These DUO-E data may offer oncologists novel avenues to enhance outcomes for endometrial cancer patients.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “The treatment options for most patients with advanced endometrial cancer are limited, especially for those with mismatch repair proficiency, and have not changed for many years. We are delighted that these DUO-E data show meaningful clinical improvements for patients when Imfinzi and Lynparza are combined or when Imfinzi is added alone. We look forward to discussing these data with global regulatory authorities and bringing these important new treatment approaches to patients as soon as possible.