Lynparza (olaparib) and Imfinzi (durvalumab)demonstrated strong clinical benefit and more than doubled median duration of response vs. chemotherapy in patients with mismatch repair proficient advanced or recurrent endometrial cancer

These results will be 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 Lynparza and Imfinzi 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 Lynparza and Imfinzi, 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.

Imfinzi plus chemotherapy followed by Imfinzi monotherapy (Imfinzi 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 Lynparza and Imfinzi 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 Imfinzi 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 Lynparza further enhances the effect of checkpoint inhibition in endometrial cancer.”

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

DUO-E: The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi (durvalumab) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy versus platinum-based chemotherapy alone as a treatment for patients with newly diagnosed advanced or recurrent endometrial cancer. The DUO-E trial randomised 699 patients with newly diagnosed advanced or recurrent epithelial endometrial carcinoma to receive either Imfinzi (1120mg) or placebo, given every three weeks in addition to standard-of-care platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg) or placebo every four weeks as maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day]) or placebo until disease progression.

The dual primary endpoint was progression-free survival (PFS) of each treatment arm versus standard of care. Key secondary endpoints included overall survival (OS), safety and tolerability. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. Mismatch repair deficient (dMMR) status reflects an inability to correct DNA replication errors and therefore results in an increased risk of cancer, while mismatch repair proficient (pMMR) status indicates when DNA repair pathways remain intact and where the mismatch repair pathway is active and functional. The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.