The combination of ICIs and chemotherapy is a standard of care for advanced endometrial cancer, but not all patients respond. Several researchers at the 2025 ASCO Annual Meeting presented data evaluating prognostic markers of response and the efficacy of novel therapies for advanced endometrial cancer.

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Following these presentations, featured expert Ramez N. Eskander, MD, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Clinical perspectives from Dr Eskander on these findings are presented here.

There was an interesting oral abstract presentation at ASCO 2025 by Shannon Neville Westin, MD, MPH, FACOG, that looked at the impact of longitudinal changes in circulating tumor DNA (ctDNA) in patients with newly diagnosed or advanced and recurrent endometrial cancer who were enrolled in the DUO-E study (abstract 5512). Patients were treated with carboplatin and paclitaxel alone vs carboplatin and paclitaxel plus durvalumab vs carboplatin and paclitaxel plus durvalumab with or without olaparib. This post hoc analysis showed that the presence of ctDNA at baseline was associated with a shorter progression-free survival across all treatment arms. It may seem intuitive that ctDNA is reflective of tumor burden, but this is really the first time that it has been shown as part of a larger clinical trial.

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Not only does the presence of ctDNA appear to be prognostic but we may also be able to understand the differential benefit of treatment by ctDNA clearance. Just with chemotherapy and immunotherapy alone, fewer patients developed evidence of ctDNA progression, and, when olaparib was added, more patients cleared ctDNA over time. These are hypothesis-generating data, and we are not able to use them to inform what we do in clinical practice. However, these data may help inform the design of future clinical trials aiming to understand how we can potentially use ctDNA to identify the patient populations at higher risk for disease recurrence and those that may benefit from dose escalation as we look at new treatment strategies.

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At ASCO 2025, there was another ctDNA-related study in the gynecology space presented by Jyoti Mayadev, MD, evaluating the relevance of ctDNA as a prognostic factor for patients with cervical cancer treated in the CALLA trial (abstract 5502). The reason I bring these up together is that both trials found that ctDNA appears to be prognostic for clinical outcome. In the analysis of patients from the CALLA study, those with cervical cancer who were ctDNA positive at the completion of chemoradiation clinically did much worse than those who had cleared ctDNA.

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Also at this year’s ASCO meeting, Xiaohua Wu, MD, PhD, presented a poster reporting the results from an ad hoc analysis of the serous carcinoma subgroup from the FRUSICA-1 study, which looked at the combination of the VEGFR inhibitor fruquintinib and the anti–PD-1 monoclonal antibody sintilimab in patients with advanced solid tumors (abstract 5596). The objective response rate was 37% in patients with mismatch repair–proficient disease. This is similar to the objective response rate reported for lenvatinib plus pembrolizumab in Study 309/KEYNOTE-775, which led to the US Food and Drug Administration (FDA) approval of this regimen for patients with advanced endometrial cancer that is mismatch repair proficient.

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Finally, a poster by Judong Li and colleagues presented at ASCO 2025 reported on the efficacy and safety of HB0025, an anti–PD-L1/VEGF bsAb that is being tested in combination with chemotherapy for the first-line treatment of patients with advanced or recurrent endometrial cancer (abstract 5602). After a median follow-up of only 5.7 months, which is a very early analysis and may not be informative, the efficacy data were not very different from what we have seen with the combination of chemotherapy and immunotherapy. That being said, there may still be a space for bsAbs such as HB0025 in the treatment of endometrial cancer, but we need to figure out the appropriate control arm for studies that evaluate this and benchmarks to use for efficacy.