The panel reflects on the most important unanswered questions and future directions in endometrial cancer. Dr. Konecny highlights the promise of molecularly stratified treatment approaches targeting HER2, TROP2, B7-H4, and hormonal signaling pathways, drawing parallels to successes achieved in breast cancer.
Dr. Thaker reviews the immune-related adverse event profile associated with checkpoint inhibitor therapy in endometrial cancer, describing the most commonly encountered toxicities in clinical practice, including hypothyroidism, hyperthyroidism, colitis, and arthralgias.
Dr. Redfern provides a detailed, clinically practical overview of mismatch repair and microsatellite instability testing in endometrial cancer, explaining the mechanistic differences between immunohistochemistry—which assesses protein expression of MLH1, PMS2, MSH2, and MSH6—and next-generation sequencing or PCR-based microsatellite instability testing.
The panel surveys the clinical trial landscape and emerging therapeutic strategies for patients with recurrent endometrial cancer, particularly those who have progressed on frontline checkpoint inhibitor–based therapy.
Upfront biomarker testing reshapes endometrial cancer care, guiding targeted and immune therapy—and exposing gaps in second-line options.
New SGO 2026 data shows frontline checkpoint inhibitors deliver 4-year survival gains and near-zero relapse after two years in DMMR cancers.
SGO 2026 data shows frontline checkpoint inhibitors in dMMR gynecologic cancer drive flat survival curves, hinting at cure and less chemo.
Dr. Konecny reviews the design and key efficacy findings of the RUBY trial, the first large randomized study to evaluate dostarlimab in combination with carboplatin and paclitaxel as frontline therapy for advanced or recurrent endometrial cancer. He describes the eligibility criteria, dosing schedule, and the striking outcomes observed in both mismatch repair–deficient and mismatch repair–proficient patient populations, including a approximately 70% risk reduction in progression-free survival in the deficient group and a statistically significant 25% risk reduction in the proficient group. Dr. Wenham and Dr. Konecny also contrast the RUBY and NRG-GY018 trial designs. Dr. Redfern then addresses how these results translate to real-world populations, citing evidence presented at ASCO 2025 demonstrating comparable outcomes, and shares her own clinical experience incorporating dostarlimab into routine practice.
Moderator Robert M. Wenham, MD, MS, opens by welcoming panelists Premal H. Thaker, MD, MS, Tiffany M. Redfern, MD, FACOG, and Gottfried E. Konecny, MD, before setting the stage for the discussion. Dr. Thaker reviews the pre-2024 treatment landscape in advanced and recurrent endometrial cancer, including the establishment of paclitaxel plus carboplatin as standard-of-care chemotherapy through GOG 209. She then outlines the pivotal shift brought about by the addition of immune checkpoint inhibitors to chemotherapy, highlighting the RUBY, NRG-GY018, and DUO-E trials and summarizing the FDA approvals that emerged from each. The panel briefly distinguishes the indications across regimens, noting that approval for the durvalumab-plus-olaparib combination was limited to patients with mismatch repair–deficient disease, setting the stage for deeper discussion of individual trial data.
Panelists discuss how emerging antibody-drug conjugates targeting B7-H4 and folate receptors are showing unprecedented 40% to 50% response rates in recurrent endometrial cancer, representing a paradigm shift from historical treatment limitations while highlighting the exciting but challenging landscape of sequencing multiple novel therapies.
Panelists discuss how the DUO trial demonstrates the benefit of durvalumab in adjuvant endometrial cancer treatment and suggests potential value of adding olaparib in specific subgroups like mismatch repair–proficient patients, though emphasizing the need for confirmatory studies before routine clinical implementation.
Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss ongoing research to watch in ovarian cancer.
Panelists discuss how the RUBY trial’s real-world data confirms the efficacy of dostarlimab maintenance therapy and surprisingly shows improved quality of life outcomes with delayed time to deterioration compared to placebo, providing confidence in using immunotherapy maintenance despite potential adverse effects.
Panelists discuss how selinexor shows remarkable efficacy in patients with mismatch repair–proficient endometrial cancer, with 40-month progression-free survival compared to 5 months with standard care, while emphasizing the importance of ongoing clinical trials to validate biomarker-driven treatment decisions.
Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss data for neoadjuvant IMNN-001 plus chemotherapy in advanced epithelial ovarian cancer.
Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss data for relacorilant plus nab-paclitaxel in platinum-resistant ovarian cancer.
Panelists discuss how endometrial cancer treatment has been revolutionized through molecular subtyping into 4 distinct groups (POLE hypermutated, microsatellite instability-high, p53 mutated, and no specific molecular pathology), enabling personalized treatment approaches based on tumor biology rather than just staging.
Panelists discuss how the field is expanding with newer antibody-drug conjugates targeting TROP2, combination immunotherapy approaches, and the critical importance of HPV vaccination as prevention, while addressing social barriers to complex treatment regimens.
Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss data for radical up-front surgery in advanced ovarian cancer from the TRUST trial.
Panelists discuss how tisotumab vedotin represents a practice-changing but modest improvement in cervical cancer treatment, with only 1.5-month progression-free survival benefit and notable ocular toxicities, while emphasizing the need for better patient access to required ophthalmologic monitoring.
Panelists discuss how cervical cancer treatment guidelines have rapidly evolved to incorporate pembrolizumab across multiple settings, from locally advanced disease with positive nodes to metastatic disease, while emphasizing the importance of comprehensive biomarker testing including PD-L1 and HER2 status for optimal treatment selection.
Panelists discuss how the recent approval of avutometinib plus defactinib for KRAS-mutated low-grade serous ovarian cancer addresses a significant unmet need in this lethal disease, with the dual FAK/MEK inhibition approach showing impressive response rates despite requiring careful toxicity management.
Panelists discuss how the emerging pipeline of folate receptor-targeted antibody-drug conjugates, including rinatabart sesutecan (Rina-S) and other novel compounds, offers diverse payload options and potentially broader patient eligibility with different toxicity profiles, though sequencing strategies remain to be determined.
Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss data for dostarlimab plus niraparib in advanced ovarian cancer.
Panelists discuss how mirvetuximab soravtansinerepresents a significant advancement for platinum-resistant ovarian cancer with folate receptor alpha expression, providing unprecedented overall survival benefits despite manageable ocular toxicities that are reversible with proper monitoring and dose modifications.
Panelists discuss how the frontline immunotherapy landscape is evolving with promising but not yet practice-changing data from the KEYNOTE and FIRST trials, suggesting potential benefits when combining pembrolizumab with PARP inhibitors in specific biomarker-defined subgroups of patients with ovarian cancer.
Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss how ADCs could continue to reshape ovarian cancer management.
Panelists discuss how NCCN guidelines structure treatment options for advanced ovarian cancer around bevacizumab decisions and HRD status, with most experts favoring PARP inhibitor maintenance therapy for 2 to 3 years while carefully monitoring for long-term toxicities like MDS and secondary leukemias.
Panelists discuss how molecular testing approaches in advanced ovarian cancer should include comprehensive upfront biomarker assessment including HRD testing, folate receptor testing, PD-L1, and HER2 evaluation, combined with germline genetic counseling to guide treatment decisions and maintenance therapy strategies.
Gottfried Konecny, MD, discusses the importance of evaluating PROs in patients with platinum-resistant ovarian cancer receiving mirvetuximab soravtansine.
August 3rd 2018
