Leslie M. Randall, MD

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.

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.

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.

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.

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.

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.

The panel closes their discussion by highlighting challenges in the treatment of cervical cancer, emphasizing the need for more focus on clinical trials and therapies, as well as addressing disparities in cancer care, particularly for patients of color.

Bradley Monk, MD, shares the promising potential of anti-HER2 therapy in cervical cancer and discusses encouraging results from recent trials, emphasizing the importance of testing for HER2 and considering anti-HER2 antibody drug conjugates as a treatment option.

Experts in gynecologic oncology discuss the positive results of TV-301, a confirmatory trial for TV-204, raising the possibility of moving tisotumab vedotin earlier in the treatment of patients with cervical cancer, and the potential to combine it with pembrolizumab.

Experts detail the management of ocular toxicity associated with tisotumab vedotin in patients with cervical cancer, emphasizing the need for eye care professionals and a team approach, along with addressing peripheral neuropathy.

Dana M. Chase, MD, FACOG, discusses the antibody-drug conjugate tisotumab vedotin including its mechanism of action, its accelerated approval for patients with recurrent cervical cancer and at least one prior line of therapy, and the management of toxicities such as neuropathy and pneumonitis.

Leslie M. Randall, MD, reviews updates to the NCCN guidelines for cervical cancer, including the use of pembrolizumab in the second and third-line settings, the results of the KEYNOTE-826 trial, and the potential role of induction chemotherapy with weekly carboplatin and paclitaxel in the treatment of locally advanced cervical cancer.

David M. O’Malley, MD, discusses cervical cancer epidemiology, risk factors, and diagnosis, highlighting the importance of HPV vaccinations, regular PAP smears, and the use of various biomarkers for treatment decision making.

Experts are enthusiastic about the potential of antibody drug conjugates to de-escalate therapy and reduce toxicity in advanced and recurrent endometrial cancer treatment, with a focus on the importance of diversity plans in clinical trials to ensure broader applicability.

The panel highlights recent data on antibody drug conjugates targeting TROP2 in patients with advanced or recurrent endometrial cancer and the need for dose optimization.

Key opinion leaders share excitement about antibody-drug conjugates targeting HER2 in advanced or recurrent endometrial cancer, and debate optimal HER2 testing methods, with some preferring gastric cancer scoring criteria over breast cancer criteria.

The panel reviews results from the ATTEND and DUO-E trials in advanced endometrial cancer, suggesting pembrolizumab remains the standard for the dMMR patient subset while combinations with PARP inhibitors may improve outcomes in pMMR.

Dr Thomas C. Krivak highlights key data from the GY018 trial investigating chemotherapy plus pembrolizumab in both dMMR and pMMR advanced endometrial cancer, confirming and extending the findings from the RUBY trial supporting pembrolizumab's approval and use in both dMMR and pMMR populations.

Thomas C. Krivak, MD, shares the positive results from the RUBY trial of pembrolizumab plus chemotherapy followed by maintenance in patients with dMMR advanced endometrial cancer, supporting its approval and use in this population.

David M. O’Malley, MD, details the definition of dMMR (mismatch repair deficiency), its prevalence in advanced endometrial cancer, and current treatment approaches for dMMR patients, with a focus on the potential for cure in recurrent/metastatic dMMR patients based on clinical trial data.

The panel discusses factors to consider when determining best treatment options for patients with recurrent or advanced endometrial cancer, including traditional clinical trial endpoints, cost, chance for cure versus disease control, and most importantly, patient preference.

Key opinion leaders review recent updates to the NCCN guidelines for treating recurrent and advanced endometrial cancer, including biomarker testing and targeted therapies like dostarlimab and trastuzumab.