Lynparza Combo May Fill Gap in Endometrial Cancer Treatment: AstraZeneca

AstraZeneca recently announced that the combined use of Lynparza (olaparib) and Imfinzi (durvalumab) has significantly increased the median response duration in individuals with endometrial cancer that has mismatch repair proficiency.

This discovery is based on findings from a Phase III clinical trial which studied the impact of administering the checkpoint inhibitor Imfinzi and the PARP inhibitor Lynparza post-chemotherapy in patients suffering from advanced or recurring endometrial cancer. Preliminary data from this trial was shared by AstraZeneca in October 2023, highlighting a 45% reduction in the risk of disease progression or mortality when compared to chemotherapy as a standalone treatment.

Further insights from the DUO-E trial were unveiled at a conference held by the Society of Gynecologic Oncology on Women’s Cancer in San Diego. The presentation centered on a post-hoc analysis that categorized the trial participants based on whether their cancer was mismatch repair proficient or deficient.

Historically, checkpoint inhibitors have demonstrated higher efficacy in mismatch repair deficient (dMMR) endometrial cancer patients, which has led to the FDA approving Merck’s Keytruda (pembrolizumab) and GSK’s Jemperli (dostarlimab) for this specific patient group.

The DUO-E trial included both dMMR and mismatch repair proficient (pMMR) patients. The data was divided to analyze the two subpopulations separately, revealing that the Lynparza-Imfinzi combination was notably more effective in the dMMR group. The median overall survival for the dMMR chemotherapy control group was 23.7 months, whereas the trial is yet to determine the median overall survival for those receiving Imfinzi alone or in combination with Lynparza.

In the dMMR group, the median response duration was 10.5 months with chemotherapy and 29.9 months with the Lynparza-Imfinzi combination. The Imfinzi-only group has not yet reached the median response duration.

While the impact of adding Lynparza to Imfinzi in dMMR patients is not definitive, as some patients responded to the PD-1 checkpoint inhibitor alone, Lynparza seems to have a more pronounced effect in pMMR patients. The median response durations in the chemotherapy, Imfinzi, and Lynparza combination groups were 7.6 months, 10.6 months, and 18.7 months, respectively.

AstraZeneca observed a similar trend in progression-free survival (PFS) data, with the median PFS increasing from 9.7 months and 9.9 months in the chemotherapy and Imfinzi groups to 15.0 months in the Lynparza combination group. The median overall survival for the Imfinzi and Lynparza combination pMMR arms has not yet been reached, and in the chemotherapy pMMR group, it was 25.9 months.

The findings suggest that the Lynparza-Imfinzi combination could play a significant role in treating pMMR endometrial cancer, where there is a significant unmet need due to the reduced effectiveness of checkpoint inhibitors. AstraZeneca has submitted the DUO-E trial results to regulatory authorities in the U.S., Europe, and Japan for review.