Plain language summary of results from the DUO-E study: durvalumab given with or without olaparib in patients with advanced endometrial cancer

Plain Language Summary: What is this summary about? There are only a few current treatment options for people with newly diagnosed advanced or recurrent endometrial cancer (cancer that has returned). The DUO-E study is testing an immunotherapy, durvalumab, and a targeted therapy, olaparib, in people with newly diagnosed advanced endometrial cancer or recurrent endometrial cancer. Durvalumab blocks the activity of a protein called PD-L1 (programmed death-ligand 1). This makes cancer cells more susceptible to being killed by immune cells. Olaparib inhibits a protein called PARP (poly [ADP-ribose] polymerase), thereby stopping cancer cells from being able to repair their DNA. This can cause cancer cells to die or make them more visible to the immune system. Mismatch repair (MMR) is a DNA repair mechanism, and patients with endometrial cancer can be defined as having tumors that are able to carry out mismatch repair (mismatch repair proficient [pMMR]) or are not able to carry out mismatch repair (mismatch repair deficient [dMMR]). DUO-E enrolled people with either mismatch repair proficient (pMMR) or mismatch repair deficient (dMMR) tumors. DUO-E investigated whether chemotherapy + durvalumab followed by either durvalumab or durvalumab + olaparib can improve outcomes compared with chemotherapy alone. What are the key takeaways? For all the people in DUO-E, the risk of disease progression (the cancer growing, spreading, or getting worse) or death was reduced with chemotherapy + durvalumab followed by either durvalumab or durvalumab + olaparib, compared with chemotherapy alone. In terms of reducing the risk of disease progression or death, the greatest benefit for chemotherapy + durvalumab compared with chemotherapy alone was seen in people with tumors that were mismatch repair deficient (dMMR); for people with tumors that were mismatch repair proficient (pMMR), the addition of olaparib further enhanced the benefit seen with durvalumab. Side effects of the treatments were manageable and generally consistent with the known side effects of the drugs when used alone. What were the main conclusions reported by the researchers? Chemotherapy + durvalumab followed by either durvalumab or durvalumab + olaparib represent new treatment options for people with newly diagnosed advanced or recurrent endometrial cancer. Clinical trial number: NCT04269200.