ASCO 2025: key highlights in endometrial cancer

Summary The 2025 ASCO Annual Meeting did not present immediately practice-changing results in endometrial cancer but showcased substantial progress across multiple therapeutic strategies. A phase II trial combining letrozole, abemaciclib, and metformin in recurrent, ER-positive disease (ER: estrogen receptor) demonstrated an objective response rate of 32% and a median progression-free survival (PFS) of 19.4 months, with activity confined to tumors without p53 abnormalities and responses independent of prior endocrine therapy. Molecular profiling suggested potential predictive and resistance biomarkers. Post hoc circulating tumor DNA (ctDNA) analysis from the phase III DUO‑E trial showed that baseline ctDNA correlated with poorer PFS. Adding durvalumab to chemotherapy resulted in faster ctDNA clearance, while maintenance olaparib further reduced ctDNA detection in non-MMR-deficient tumors (MMR: mismatch repair), supporting additional benefit in this subgroup. Several phase II studies highlighted synergistic activity between PD-L1 inhibition and anti-angiogenic therapy. A bispecific PD-L1/VEGF antibody (HB0025) combined with chemotherapy achieved high response rates and encouraging short-term PFS with manageable toxicity. Similarly, adding anlotinib to PD-L1 inhibition and chemotherapy significantly improved PFS compared with immunotherapy alone. Finally, early-phase studies of novel agents, including a selective CDK2 inhibitor and a folate receptor‑α targeting antibody drug conjugate, demonstrated promising antitumor activity with acceptable safety profiles in heavily pretreated patients. Overall, ASCO 2025 underscored meaningful therapeutic advances and biomarker-driven refinement.