The Future of Endometrial Cancer Therapeutics: Phase 3 Trials of ADCs and Beyond

From Carcinosarcoma to Circulating Tumor DNA: The Importance of Investigator-Initiated Research in Endometrial Cancer

Drs Ursula A. Matulonis and Stephanie Lheureux discuss the importance of investigator-initiated clinical trials in endometrial cancer, research on carcinosarcoma, and ctDNA. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s3-ep4-2026a10006ie [https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s3-ep4-2026a10006ie]. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Endometrial Carcinoma https://emedicine.medscape.com/article/254083-overview [https://emedicine.medscape.com/article/254083-overview] Advances in Antibody-Drug Conjugates for Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/40111079/ [https://pubmed.ncbi.nlm.nih.gov/40111079/] TCGA Molecular Prognostic Groups of Endometrial Carcinoma: Current Knowledge and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/36232987/ [https://pubmed.ncbi.nlm.nih.gov/36232987/] Translational Randomized Phase II Trial of Cabozantinib in Combination With Nivolumab in Advanced, Recurrent, or Metastatic Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/35288469/ [https://pubmed.ncbi.nlm.nih.gov/35288469/] Elucidating Divergent Biology in Uterine Carcinosarcoma https://pubmed.ncbi.nlm.nih.gov/40850250/ [https://pubmed.ncbi.nlm.nih.gov/40850250/] The Immune Microenvironment in Endometrial Carcinoma: Mechanisms and Therapeutic Targeting https://pubmed.ncbi.nlm.nih.gov/40746533/ [https://pubmed.ncbi.nlm.nih.gov/40746533/] Epithelial-Mesenchymal Transition Orchestrates Tumor Microenvironment: Current Perceptions and Challenges https://pubmed.ncbi.nlm.nih.gov/40176117/ [https://pubmed.ncbi.nlm.nih.gov/40176117/] Comparative Modeling of Recent and Projected Trends in the Incidence and Mortality of Uterine Cancer https://pubmed.ncbi.nlm.nih.gov/41643197/ [https://pubmed.ncbi.nlm.nih.gov/41643197/] Genomic Landscape of ctDNA and Real-World Outcomes in Advanced Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/39417689/ [https://pubmed.ncbi.nlm.nih.gov/39417689/] Targeting CDK2 for Cancer Therapy https://pubmed.ncbi.nlm.nih.gov/40802510/ [https://pubmed.ncbi.nlm.nih.gov/40802510/] PYNNACLE Phase II Trial Assessing Rezatapopt (PC14586), a Selective p53 Reactivator, in Patients With Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation https://www.gynecologiconcology-online.net/article/S0090-8258%2825%2900347-6/abstract [https://www.gynecologiconcology-online.net/article/S0090-8258%2825%2900347-6/abstract] Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com [https://pcm.adswizz.com] for information about our collection and use of personal data for advertising.

Endometrial Cancer: SWI/SNF Complexes, GLP-1 Receptor Agonists, and the Future of Research and Treatment

Drs Ursula Matulonis and Jessica St. Laurent discuss endometrial cancer research, funding, early detection, and treatment, including the impact of GLP-1 receptor agonists. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s3-ep3-2026a10006id. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Endometrial Carcinoma https://emedicine.medscape.com/article/254083-overview [https://emedicine.medscape.com/article/254083-overview] Hereditary Breast and Ovarian Cancer (HBOC): Review of Its Molecular Characteristics, Screening, Treatment, and Prognosis https://pubmed.ncbi.nlm.nih.gov/32862296/ [https://pubmed.ncbi.nlm.nih.gov/32862296/] Shifted Assembly and Function of mSWI/SNF Family Subcomplexes Underlie Targetable Dependencies in Dedifferentiated Endometrial Carcinomas https://pubmed.ncbi.nlm.nih.gov/41116019/ [https://pubmed.ncbi.nlm.nih.gov/41116019/] Cancer Statistics, 2026 https://pubmed.ncbi.nlm.nih.gov/41528114/ [https://pubmed.ncbi.nlm.nih.gov/41528114/] Tirzepatide as an Innovative Treatment Strategy in a Pre-Clinical Model of Obesity-Driven Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/39388742/ [https://pubmed.ncbi.nlm.nih.gov/39388742/] Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes https://pubmed.ncbi.nlm.nih.gov/38967919/ [https://pubmed.ncbi.nlm.nih.gov/38967919/] GLP-1 Receptor Agonists Plus Progestins and Endometrial Cancer Risk in Nonmalignant Uterine Diseases https://pubmed.ncbi.nlm.nih.gov/41665904/ [https://pubmed.ncbi.nlm.nih.gov/41665904/] TCGA Molecular Prognostic Groups of Endometrial Carcinoma: Current Knowledge and Future Perspectives https://pubmed.ncbi.nlm.nih.gov/36232987/ [https://pubmed.ncbi.nlm.nih.gov/36232987/] Menstrual Cup for Early Endometrial Cancer Detection in Lynch Syndrome (SCREEN-CUP) https://clinicaltrials.gov/study/NCT07220239 [https://clinicaltrials.gov/study/NCT07220239] Circulating Tumor DNA in Endometrial Cancer: Clinical Significance and Implications https://pubmed.ncbi.nlm.nih.gov/39955181/ [https://pubmed.ncbi.nlm.nih.gov/39955181/] PTEN Mutations as Predictive Marker for the High-Grade Endometrial Cancer Development in Slovak Women https://pubmed.ncbi.nlm.nih.gov/36592448/ [https://pubmed.ncbi.nlm.nih.gov/36592448/] Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com [https://pcm.adswizz.com] for information about our collection and use of personal data for advertising.

Route 66 SPORE and the Direction of Endometrial Cancer Research

Drs Ursula A. Matulonis and David G. Mutch discuss past and present endometrial cancer research, including the Route 66 SPORE. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s3-ep2-2026a10006ic [https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s3-ep2-2026a10006ic]. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Endometrial Carcinoma https://emedicine.medscape.com/article/254083-overview [https://emedicine.medscape.com/article/254083-overview] Route 66 Endometrial Cancer SPORE https://dctd.cancer.gov/research/spores/state/wustl-endometrial [https://dctd.cancer.gov/research/spores/state/wustl-endometrial] Final Analysis of RTOG 9708: Adjuvant Postoperative Irradiation Combined With Cisplatin/Paclitaxel Chemotherapy Following Surgery for Patients With High-Risk Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/16545437/ [https://pubmed.ncbi.nlm.nih.gov/16545437/] Pelvic Radiation With Concurrent Chemotherapy Compared With Pelvic and Para-Aortic Radiation for High-Risk Cervical Cancer https://pubmed.ncbi.nlm.nih.gov/10202164/ [https://pubmed.ncbi.nlm.nih.gov/10202164/] Surgical-Pathological Findings in Type 1 and 2 Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study on GOG-210 Protocol https://pubmed.ncbi.nlm.nih.gov/28392124/ [https://pubmed.ncbi.nlm.nih.gov/28392124/] GOG Foundation https://www.gog.org/ [https://www.gog.org/] The Latest Updates in Translational Science at NRG Oncology (October 2025) https://www.nrgoncology.org/Home/News/Post/the-latest-updates-in-translational-science-at-nrg-oncology-october-2025/ [https://www.nrgoncology.org/Home/News/Post/the-latest-updates-in-translational-science-at-nrg-oncology-october-2025/] Adjuvant Chemotherapy Plus Radiation for Locally Advanced Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/31189035/ [https://pubmed.ncbi.nlm.nih.gov/31189035/] Adjuvant Chemoradiotherapy Versus Radiotherapy Alone in Women With High-Risk Endometrial Cancer (PORTEC-3): 10-Year Clinical Outcomes and Post-Hoc Analysis by Molecular Classification From a Randomised Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/40921169/ [https://pubmed.ncbi.nlm.nih.gov/40921169/] FIGO Staging of Endometrial Cancer: 2023 https://pubmed.ncbi.nlm.nih.gov/37337978/ [https://pubmed.ncbi.nlm.nih.gov/37337978/] Practical Guidance for Assessing and Reporting Lymphovascular Space Invasion (LVSI) in Endometrial Carcinoma https://pubmed.ncbi.nlm.nih.gov/38937066/ [https://pubmed.ncbi.nlm.nih.gov/38937066/] Surgical Pathologic Spread Patterns of Endometrial Cancer. A Gynecologic Oncology Group Study https://pubmed.ncbi.nlm.nih.gov/3652025/ [https://pubmed.ncbi.nlm.nih.gov/3652025/] Integrated Genomic Characterization of Endometrial Carcinoma https://pubmed.ncbi.nlm.nih.gov/23636398/ [https://pubmed.ncbi.nlm.nih.gov/23636398/] AXL Inhibition Improves the Therapeutic Efficacy of Trastuzumab in High-Risk Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/41270342/ [https://pubmed.ncbi.nlm.nih.gov/41270342/] Patient-Derived Xenograft Mouse Models: A High Fidelity Tool for Individualized Medicine https://pubmed.ncbi.nlm.nih.gov/30655732/ [https://pubmed.ncbi.nlm.nih.gov/30655732/] Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com [https://pcm.adswizz.com] for information about our collection and use of personal data for advertising.

The Future of Endometrial Cancer Therapeutics: Phase 3 Trials of ADCs and Beyond

Drs Ursula Matulonis and Brian Slomovitz discuss phase 3 trials of ADCs in endometrial cancer and what's to come in the field of endometrial cancer therapeutics. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s3-ep1-2026a10006ib [https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s3-ep1-2026a10006ib]. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Endometrial Carcinoma https://emedicine.medscape.com/article/254083-overview [https://emedicine.medscape.com/article/254083-overview] B7 Homolog 4 (B7-H4)-Directed Agents in Oncology Clinical Trials: A Review https://pubmed.ncbi.nlm.nih.gov/40212845/ [https://pubmed.ncbi.nlm.nih.gov/40212845/] Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial https://pubmed.ncbi.nlm.nih.gov/37870536/ [https://pubmed.ncbi.nlm.nih.gov/37870536/] Standardized Pathology Report for HER2 Testing in Compliance With 2023 ASCO/CAP Updates and 2023 ESMO Consensus Statements on HER2-Low Breast Cancer https://pubmed.ncbi.nlm.nih.gov/37770765/ [https://pubmed.ncbi.nlm.nih.gov/37770765/] Puxitatug Samrotecan (AZD8205) Monotherapy vs Chemotherapy in B7-H4-selected Endometrial Cancer (Bluestar-Endometrial01) https://clinicaltrials.gov/study/NCT07044336 [https://clinicaltrials.gov/study/NCT07044336] Safety and Efficacy of Mirvetuximab Soravtansine, a Folate Receptor Alpha (FRα)-Targeting Antibody-Drug Conjugate (ADC), in Combination With Bevacizumab in Patients With Platinum-Resistant Ovarian Cancer https://pubmed.ncbi.nlm.nih.gov/36736157/ [https://pubmed.ncbi.nlm.nih.gov/36736157/] First in Human Study of IMGN151 in Recurrent Gynaecological Cancers https://clinicaltrials.gov/study/NCT05527184 [https://clinicaltrials.gov/study/NCT05527184] DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2-Expressing (IHC 3+/2+), Mismatch Repair Proficient (pMMR) Endometrial Cancer (DE-01) https://clinicaltrials.gov/study/NCT06989112 [https://clinicaltrials.gov/study/NCT06989112] Pembrolizumab Plus Chemotherapy in Advanced or Recurrent Endometrial Cancer: Overall Survival and Exploratory Analyses of the NRG GY018 Phase 3 Randomized Trial https://pubmed.ncbi.nlm.nih.gov/40044930/ [https://pubmed.ncbi.nlm.nih.gov/40044930/] The GOG Highlight Reel July 2025 https://www.gog.org/wp-content/uploads/2025/08/GOG-Highlight-Reel-July-2025-Presentation-7.26.25.pdf [https://www.gog.org/wp-content/uploads/2025/08/GOG-Highlight-Reel-July-2025-Presentation-7.26.25.pdf] Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection https://pubmed.ncbi.nlm.nih.gov/38892080/ [https://pubmed.ncbi.nlm.nih.gov/38892080/] Phase II Trial of Ribociclib Plus Letrozole in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube, or Peritoneum: A GOG Partners Trial (GOG 3026) https://pubmed.ncbi.nlm.nih.gov/41385758/ [https://pubmed.ncbi.nlm.nih.gov/41385758/] A Phase II Study of Frontline Paclitaxel/Carboplatin/Bevacizumab, Paclitaxel/Carboplatin/Temsirolimus, or Ixabepilone/Carboplatin/Bevacizumab in Advanced/Recurrent Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/29804638/ [https://pubmed.ncbi.nlm.nih.gov/29804638/] Mutated p53 Portends Improvement in Outcomes When Bevacizumab Is Combined With Chemotherapy in Advanced/Recurrent Endometrial Cancer: An NRG Oncology Study https://pubmed.ncbi.nlm.nih.gov/33541735/ [https://pubmed.ncbi.nlm.nih.gov/33541735/] Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer https://clinicaltrials.gov/study/NCT07198074 [https://clinicaltrials.gov/study/NCT07198074] WEE1 Inhibitor: Clinical Development https://pubmed.ncbi.nlm.nih.gov/34269904/ [https://pubmed.ncbi.nlm.nih.gov/34269904/] Palbociclib Plus Letrozole in Estrogen Receptor-Positive Advanced/Recurrent Endometrial Cancer: Double-Blind Placebo-Controlled Randomized Phase II ENGOT-EN3/PALEO Trial https://pubmed.ncbi.nlm.nih.gov/39657575/ [https://pubmed.ncbi.nlm.nih.gov/39657575/] GOG3069: Phase 2 Study of Alpelisib and Fulvestrant for PIK3CA-Mutated Estrogen Receptor (ER)-Positive Endometrioid Endometrial Cancers https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5639 [https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5639] TP004/#1561 A Phase 2, Open-Label, Single-Arm, Prospective, Multicenter Study of Nab-Sirolimus Plus Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer https://www.sciencedirect.com/science/article/pii/S1048891X24163530 [https://www.sciencedirect.com/science/article/pii/S1048891X24163530] Repositioning GLP-1 Receptor Agonists in Endometrial Cancer: Molecular Rationale, Preclinical Insights, and Translational Opportunities https://pubmed.ncbi.nlm.nih.gov/41329840/ [https://pubmed.ncbi.nlm.nih.gov/41329840/] Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com [https://pcm.adswizz.com] for information about our collection and use of personal data for advertising.

Can the Use of ADCs in Breast Cancer Teach Us About Resistance Mechanisms and Sequencing in Endometrial Cancer?

Drs Ursula A. Matulonis and Leif W. Ellisen discuss endometrial cancer and ADCs, including resistance mechanisms, ADC sequencing, what's exciting in the field, and novel payloads. Relevant disclosures can be found with the episode show notes on Medscape https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s2-ep6-2026a10008nk [https://www.medscape.com/ca8/p04/podcast-endometrial-cancer-s2-ep6-2026a10008nk]. The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Endometrial Carcinoma https://emedicine.medscape.com/article/254083-overview [https://emedicine.medscape.com/article/254083-overview] The Clinical Landscape of Antibody-Drug Conjugates in Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/39074933/ [https://pubmed.ncbi.nlm.nih.gov/39074933/] FDA Grants Accelerated Approval to Fam-Trastuzumab Deruxtecan-nxki for Unresectable or Metastatic HER2-Positive Solid Tumors https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2 [https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2] Mechanisms of Resistance to Antibody-Drug Conjugates https://pubmed.ncbi.nlm.nih.gov/36831621/ [https://pubmed.ncbi.nlm.nih.gov/36831621/] TOP1 Mutations and Cross-Resistance to Antibody-Drug Conjugates in Patients With Metastatic Breast Cancer https://pubmed.ncbi.nlm.nih.gov/39745368/ [https://pubmed.ncbi.nlm.nih.gov/39745368/] Single-Cell Analysis Technologies for Cancer Research: From Tumor-Specific Single Cell Discovery to Cancer Therapy https://pubmed.ncbi.nlm.nih.gov/37900181/ [https://pubmed.ncbi.nlm.nih.gov/37900181/] Spatial Transcriptomics for Tumor Heterogeneity Analysis https://pubmed.ncbi.nlm.nih.gov/35899203/ [https://pubmed.ncbi.nlm.nih.gov/35899203/] Exploring Circulating Tumor DNA (CtDNA) and Its Role in Early Detection of Cancer: A Systematic Review https://pmc.ncbi.nlm.nih.gov/articles/PMC10516512/ [https://pmc.ncbi.nlm.nih.gov/articles/PMC10516512/] Current and Emerging Prognostic Biomarkers in Endometrial Cancer https://pubmed.ncbi.nlm.nih.gov/35530346/ [https://pubmed.ncbi.nlm.nih.gov/35530346/] Parallel Genomic Alterations of Antigen and Payload Targets Mediate Polyclonal Acquired Clinical Resistance to Sacituzumab Govitecan in Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/34404686/ [https://pubmed.ncbi.nlm.nih.gov/34404686/] Antibody-Drug Conjugate Sacituzumab Govitecan Enables a Sequential TOP1/PARP Inhibitor Therapy Strategy in Patients With Breast Cancer https://pubmed.ncbi.nlm.nih.gov/38709212/ [https://pubmed.ncbi.nlm.nih.gov/38709212/] Antibody-Drug Conjugates as Targeted Therapy for Treating Gynecologic Cancers: Update 2025 https://pubmed.ncbi.nlm.nih.gov/39480912/ [https://pubmed.ncbi.nlm.nih.gov/39480912/] Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com [https://pcm.adswizz.com] for information about our collection and use of personal data for advertising.