Clinical Summary

• The second interim overall survival analysis of the phase 3 DUO-E/GOG-3041/ENGOT-EN10 trial demonstrated a clinically meaningful, although not statistically significant, survival benefit with durvalumab-based regimens in patients with advanced or recurrent endometrial cancer, including an 11.5-month improvement in median overall survival with durvalumab plus olaparib maintenance versus control.
• In patients with mismatch repair-deficient (dMMR) tumors, durvalumab and durvalumab plus olaparib were associated with 43% and 57% reductions in the risk of death, respectively, while patients with mismatch repair-proficient (pMMR) tumors experienced a 15% reduction in the risk of death with durvalumab plus olaparib versus control.
• No new safety signals emerged with longer follow-up, and the findings support the clinical relevance of durvalumab-based treatment strategies while underscoring the importance of mismatch repair status in evaluating outcomes and selecting therapy.

Shannon N. Westin, MD, of The University of Texas MD Anderson Cancer Center in Houston, discusses findings from the second interim overall survival analysis of the phase 3 DUO-E/GOG-3041/ENGOT-EN10 trial, presented at the 2026 ESMO Congress in Madrid, Spain. The global, randomized, placebo-controlled study evaluated carboplatin/paclitaxel chemotherapy with or without durvalumab, followed by maintenance durvalumab with or without olaparib, in patients with advanced or recurrent endometrial cancer. At approximately 52% overall survival data maturity, both durvalumab-containing treatment arms demonstrated clinically meaningful, although not statistically significant, improvements in overall survival compared with chemotherapy alone. In the intent-to-treat population, durvalumab plus olaparib was associated with a 23% reduction in the risk of death and an 11.5-month improvement in median overall survival versus control.

Subgroup analyses demonstrated differences in treatment outcomes according to mismatch repair status. Among patients with dMMR tumors, durvalumab alone was associated with a 43% reduction in the risk of death, while durvalumab plus olaparib was associated with a 57% reduction compared with control; median overall survival had not yet been reached in the combination arm. In patients with pMMR tumors, durvalumab plus olaparib demonstrated the greatest numerical survival benefit, with a 15% reduction in the risk of death and an approximately 8-month improvement in median overall survival. No new safety signals were identified, with adverse events consistent with the known safety profiles of the individual agents and only one case of myelodysplastic syndrome or leukemia reported in the durvalumab plus olaparib arm. Although the survival findings remain immature and statistically nonsignificant, they provide additional evidence supporting the potential long-term clinical benefit of durvalumab-based regimens and reinforce the importance of molecular stratification in advanced endometrial cancer treatment.

Transcript

Shannon N. Westin, MD: Hi, I'm Dr. Shannon Westin from The University of Texas MD Anderson Cancer Center, and I am here at ESMO 2026 in Madrid. I'm delighted to be presenting the interim overall survival data from our study, DUO-E.

Just to level-set and remind you, DUO-E was a global, randomized, placebo-controlled trial of chemotherapy with or without durvalumab, followed by durvalumab with or without olaparib as a maintenance strategy for advanced and recurrent endometrial cancer. We included all histologic subtypes, including carcinosarcoma. We allowed prior chemotherapy as long as it had been at least 12 months since they received it. We did stratify patients by mismatch repair deficiency, as this was an immunotherapy study, but all patients were included. Patients were randomized 1:1:1, and the dual primary endpoints were progression-free survival for the durvalumab arm versus control, as well as for the durvalumab plus olaparib arm versus control.

We already presented that DUO-E met its dual primary endpoints back at a previous ESMO, and we did see improvement in progression-free survival in both the durvalumab arm versus control as well as the durvalumab plus olaparib arm versus control.

But again, this was an immunotherapy study, so we needed to look at that mismatch repair deficiency. We couldn't just look at the intent-to-treat population.

In the mismatch repair–deficient group, we saw that durvalumab really provided the biggest benefit in regard to progression-free survival, and that makes sense. We didn't see much more improvement in progression-free survival when we added olaparib. Conversely, in the mismatch repair-proficient group, that was where durvalumab and olaparib really seemed to provide the increased progression-free survival benefit.

That gets us to where we are today. This was our second interim analysis of overall survival. We're at about 52% maturity, so not yet at our final analysis.

What we saw in the intent-to-treat population was that there was not a statistically significant, but a very clinically meaningful, improvement in overall survival in both the durvalumab arm versus control and the durvalumab plus olaparib arm versus control. In the durvalumab plus olaparib arm, we saw a 23% reduction in the risk of death overall. That was consistent with a median 11.5-month improvement in median overall survival for durvalumab plus olaparib versus control. Again, that was in an all-comers population. This is a very clinically meaningful benefit. And again, not yet statistically significant, but certainly incredibly reassuring.

We did tease out those results again by that mismatch repair deficiency status. In the mismatch repair-deficient population, we saw benefit for durvalumab versus control, about a 43% reduction in the risk of death compared to those who just got chemotherapy alone. But interestingly, even though we didn't see PFS benefit before when we gave durvalumab and olaparib to the mismatch repair-deficient group, we saw a 57% reduction in the risk of death in the population that got durvalumab plus olaparib as opposed to control.

To me, that's an incredible benefit. The median overall survival hasn't even been reached yet, and I'm very eager to see how those data mature.

Finally, in the mismatch repair-proficient group, again, we saw some benefit in overall survival for durvalumab versus control. But the biggest benefit was in the population that got durvalumab and olaparib versus control, where we saw a 15% reduction in the risk of death, which was consistent with about an 8-month improvement in median overall survival.

Really incredible data. Not yet statistically significant, but certainly very clinically meaningful and very supportive of the global regulatory approvals that we've gotten for both durvalumab and durvalumab plus olaparib in addition to chemotherapy in this patient population of advanced and recurrent endometrial cancer.

I will just make a note about safety. The good news about safety is we haven't seen any new safety signals. Really, what we see in the treatment arms is the expected adverse events for each of the individual components. Specifically, with adverse events of special interest like myelodysplastic syndrome (MDS) and leukemia, we've only had one case over the entire study in the durvalumab plus olaparib arm. Again, very reassuring safety.

Bottom line, we're really excited about these interim overall survival results, where we see a clinically meaningful, not yet statistically significant benefit for both durvalumab and durvalumab plus olaparib in addition to chemotherapy for advanced and recurrent endometrial cancer.

Thank you so much.

Source

Westin SN, Moore KN, Chon HS, et al. Durvalumab (D) plus carboplatin/paclitaxel (CP) followed by D with or without olaparib (O) in advanced/recurrent endometrial cancer (a/rEC): interim overall survival (OS) and safety from the randomised phase 3 DUO-E/GOG-3041/ENGOT-EN10 study. Presented at: ESMO Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract LBA37.