Shannon Westin, MD, MPH, MD Anderson Cancer Center, Houston, Texas, discusses translational analysis results from the DUO-E trial which assessed first-line durvalumab plus chemotherapy followed by durvalumab with or without olaparib in patients with endometrial cancer. 

Dr Westin concluded this data “further supports the use of olaparib and durvalumab in this patient population,” and also demonstrates “how ctDNA might be really helpful in monitoring and treating these patients.”

Dr Westin presented these results at the 2025 ASCO Annual Meeting in Chicago, Illinois. 

Transcript: 

Hi, my name is Dr Shannon Weston and I'm a professor of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center in Houston and I'm here at ASCO 2025, super excited to be here.

I'm going to tell you a little bit about our translational analysis of the DUO-E study. Just as a reminder, DUO-E was a study in advanced and recurrent endometrial cancer where we looked to see about the value of adding durvalumab, the PD-L1 inhibitor, to chemotherapy — both with chemo[therapy] and then followed by durvalumab maintenance. Then we had a second arm where we added olaparib to the durvalumab to see if that had any impact on improvement in survival for those patients in the maintenance setting. 

We saw that we met both of our primary end points in that primary study, so improved progression-free survival both in the durvalumab arm as compared to chemo, as well as in the durvalumab-olaparib arm as compared to chemo. But interestingly, for the durvalumab arm, the biggest impact was in mismatch repair deficient and conversely, in the durvalumab-olaparib arm, the biggest impact was in the mismatch repair proficient group. Now, with all that being said, this is all obviously very exciting, but we wanted to do a really deep dive on some of the translational data.

In about 341 of the patients, we were able to get 4 timepoints of ctDNA testing, and that included a baseline test, cycle 3 day 1 which was mid-chemo, cycle 7 day 1 which was meant to be right at the beginning of maintenance, and cycle 9 day 1 which is mid-maintenance. And this would give us a sense of really what's the incidence of patients that have a positive ctDNA and what's the impact of that, and then further, what's the impact of the treatment on ctDNA. 

The first thing we figured out is that anybody that had positive ctDNA at the beginning of treatment had a worse prognosis, they had worse progression-free survival. That was regardless of the arm that they were on, regardless of the stage, it seemed to be an independent factor, and that's really important. We didn't know that before, we don't have a lot of data like that for advanced endometrial cancer so, one bit of information that matters. But I think more excitingly is when we looked at the longitudinal data, we saw some really cool changes. 

The first was the addition of durvalumab to chemo led to higher levels of clearance of ctDNA. This means going from ctDNA-positive to ctDNA-negative. When we added durvalumab to chemo, there was a higher clearance than the chemo alone, that was pretty cool. But I think more excitingly in the mismatch repair proficient group, when we got to that maintenance setting, this is cycle 7 day 1, as compared to cycle 9 day 1 what we saw is when we added olaparib to mismatch repair proficient, they had a higher level of clearance: 35% of patients cleared their positive ctDNA in that olaparib arm as compared to chemo, so that's really exciting. That shows us this potential for novel anti-tumor activity in the maintenance setting, which is not something we've seen before. 

We're really excited about these data and what they might mean. We do think it further supports the use of olaparib and durvalumab in this patient population, but also really starts to show us how ctDNA might be really helpful in monitoring and treating these patients.

Source: 

Westin S, Moore K, Guy M, et al. Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer: Longitudinal changes in circulating tumor DNA. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 5512