Latest analysis of the results from the DUO-E Phase III trial showed durvalumab plus platinum-based chemotherapy followed by durvalumab plus olaparib, (olaparib and durvalumab arm) demonstrated an improvement in multiple key secondary efficacy endpoints, particularly in patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer compared to chemotherapy alone. 

These results were presented in a late-breaking session at the 2024 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in San Diego, California.

A post-hoc exploratory subgroup analysis assessed patients by mismatch repair (MMR) status, a biomarker of interest in endometrial cancer.

In this analysis, median duration of response (DoR) in pMMR patients in the olaparib and durvalumab arm was more than double versus the control arm (18.7 months versus 7.6).

Additional secondary endpoints showed consistent results for pMMR patients treated with olaparib and durvalumab, demonstrating a reduction in the risk of second progression or death (PFS2) by 32% for the combination versus the control arm (median not reached versus 19.5 months, HR 0.68; 95% confidence interval [CI] 0.48-0.95), and improvement in time to first and second subsequent treatments.

Durvalumab plus chemotherapy followed by durvalumab monotherapy (durvalumab arm) showed consistent benefit regardless of MMR status, with the greatest benefit observed in patients with mismatch repair deficient (dMMR) disease across all secondary endpoints, including objective response rate (ORR) (71.4%) and DoR (median not reached), versus the control arm (40.5% and 10.5 months, respectively).

In the overall trial population, results in the olaparib and durvalumab arm showed extended ORR and DoR, as well as consistently improved benefit in secondary endpoints, including overall survival (OS), time to first subsequent therapy (TFST), PFS2 and time to second subsequent therapy (TSST).

Hye Sook Chon, gynaecologic oncologist at the Moffitt Cancer Center in Tampa, Florida, and trial investigator, said, “Endometrial cancer diagnoses are rapidly rising, yet very little has changed in recent years to advance new treatments for the approximately eighty per cent of patients with advanced or recurring disease who are mismatch repair proficient. DUO-E results demonstrate the benefit of durvalumab plus chemotherapy followed by durvalumab for patients with dMMR status and provide compelling evidence for the addition of olaparib to this regimen for patients with pMMR status.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “DUO-E results have shown that adding durvalumab to chemotherapy delivers better outcomes for patients with advanced endometrial cancer. In addition, to achieve optimal clinical benefit for patients with the greatest unmet need – those with mismatch repair proficient disease – the addition of olaparib further enhances the effect of checkpoint inhibition in endometrial cancer.”

Interim OS data showed a favourable trend for the durvalumab arm and olaparib and durvalumab arm compared to the control arm in the overall trial population, irrespective of mismatch repair status.

Source: Astra Zeneca