AstraZeneca Shows Lynparza Combo Could Address Unmet Endometrial Cancer Need

AstraZeneca plant_iStock, Roland Magnusson

Pictured: AstraZeneca's production plant in Sweden/iStock, Roland Magnusson

AstraZeneca on Monday reported that the combination of Lynparza (olaparib) and Imfinzi (durvalumab) more than doubled the median duration of response in patients with mismatch repair proficient endometrial cancer.

The data come from a Phase III trial that evaluated the effect of giving the checkpoint inhibitor Imfinzi and PARP inhibitor Lynparza after chemotherapy in patients with advanced or recurrent endometrial cancer. AstraZeneca shared headline data from the trial in October 2023, when it reported that the drug combination reduced the risk of disease progression or death by 45% compared to chemotherapy alone.

Researchers presented more data from the DUO-E trial at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in San Diego. The presentation focused on a post-hoc analysis that split the trial population up based on whether they had mismatch repair proficient or deficient cancer.

Checkpoint inhibitors have previously proven more effective in patients with mismatch repair deficient (dMMR) endometrial cancer, leading to FDA approvals for Merck’s Keytruda (pembrolizumab) and GSK’s Jemperli (dostarlimab) in that subpopulation.

AstraZeneca enrolled dMMR and in patients with mismatch repair proficient (pMMR) patients in DUO-E. Dividing the dataset into two subpopulations showed that the Lynparza-Imfinzi combination was most effective in dMMR. Median overall survival (OS) in the dMMR chemotherapy control arm was 23.7 months. The trial is yet to reach the median OS in the cohorts that received Imfinzi as a single agent or the checkpoint inhibitor in combination with Lynparza.

The median duration of response in dMMR patients was 10.5 months in the chemotherapy arm and 29.9 months in the Lynparza-Imfinzi combination cohort. The Imfinzi arm is yet to reach the median duration of response.

While the effect of adding Lynparza to Imfinzi in dMMR is unclear, with patients responding to the PD-1 checkpoint inhibitor alone, the PARP inhibitor appears to have a bigger effect in pMMR. The median durations of response in the chemotherapy, Imfinzi and Lynparza combination cohorts were 7.6 months, 10.6 months and 18.7 months, respectively. 

AstraZeneca tracked a similar pattern in the progression-free survival (PFS) data. Median PFS rose from 9.7 months and 9.9 months, respectively, in the chemotherapy and Imfinzi cohorts to 15.0 months in the Lynparza combination group. The Imfinzi and Lynparza combination pMMR arms are yet to reach median OS. In the chemotherapy pMMR group, the median OS was 25.9 months.

The results suggest there may be a role for the Lynparza-Imfinzi combination in pMMR, a setting where there is unmet need because checkpoint inhibitors are less effective. AstraZeneca has submitted filings for DUO-E to regulators in the U.S., Europe and Japan.

Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.

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