AstraZeneca unveiled encouraging results from their Phase III trial, DUO-E, investigating the efficacy of combining Lynparza (olaparib) and Imfinzi (durvalumab) in advanced or recurrent endometrial cancer patients. Data presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer highlighted a significant improvement in the median duration of response among patients with mismatch repair proficient (pMMR) endometrial cancer.
Imfinzi (durvalumab) is a human monoclonal antibody targeting the PD-L1 protein, disrupting its interaction with PD-1 and CD80 proteins, thus countering tumor immune evasion. Lynparza, a first-in-class PARP inhibitor, blocks DNA damage response in cells with deficiencies in homologous recombination-related genes, like BRCA1/BRCA2 mutations or those induced by other agents.
Previously, AstraZeneca reported a 45% reduction in disease progression or death risk with the Lynparza-Imfinzi combination versus chemotherapy alone. However, recent analysis stratified patients by MMR status, including both dMMR and pMMR subjects. While checkpoint inhibitors are typically more effective in dMMR endometrial cancer, this trial assessed both subsets.
In the dMMR subgroup, the Lynparza-Imfinzi combination displayed significant benefits, doubling the median duration of response compared to chemotherapy alone. Notably, median overall survival (OS) was significantly extended in the dMMR group with combination therapy, while OS outcomes for the Imfinzi-Lynparza combo in pMMR patients are pending.
Additionally, Imfinzi monotherapy showed modest efficacy, but the addition of Lynparza notably enhanced outcomes in pMMR patients. Median response durations and progression-free survival (PFS) were markedly improved with the Lynparza combination versus chemotherapy or Imfinzi alone in the pMMR cohort.
These findings suggest a potential role for the Lynparza-Imfinzi combination in addressing the unmet needs of pMMR endometrial cancer patients, where checkpoint inhibitors have limited efficacy. AstraZeneca has initiated regulatory filings for DUO-E in the U.S., Europe, and Japan, indicating their commitment to introducing this potentially transformative treatment option globally.