Thomas C. Krivak, 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.

Panelists discuss recent data on emerging antibody-drug conjugates in advanced and recurrent endometrial cancer, including anti-TROP2 agents like sacituzumab govitecan from the TROPiCS-03 trial, datopotamab deruxtecan from TROPION-PanTumor03, and sacituzumab tirumotecan, as well as anti–folate receptor agents like luveltamab tazevibulin and rinatabart sesutecan, while offering future perspectives and closing thoughts on the evolving role of these agents in the treatment landscape for endometrial cancer.

Panelists discuss the recent tumor-agnostic approval of trastuzumab deruxtecan (T-DXd) based on findings from the DESTINY-PanTumor02 trial, exploring its implications for treatment approaches in advanced endometrial cancer, how to integrate T-DXd into treatment algorithms, patient selection criteria, and which patients are most likely to benefit from this therapy compared to lenvatinib/pembrolizumab.

Panelists discuss emerging data from ongoing trials evaluating innovative combination strategies for endometrial cancer, including insights from the LEAP trial (pembrolizumab + lenvatinib) and the KEYNOTE-B21 trial (pembrolizumab + chemotherapy with or without radiotherapy). They also address treatment considerations for patients with sentinel lymph node–positive disease.

Panelists discuss recent updates from the DUO-E trial, highlighting key efficacy and safety data that led to the FDA’s approval of durvalumab for endometrial cancer while examining how this new indication influences treatment strategies for advanced or recurrent cases.

Panelists review available treatment options for recurrent endometrial cancer, discussing their typical treatment approaches and the factors influencing treatment selection. Panelists also address insights from the RUBY trial, its updates, and the expanded FDA indication for dostarlimab, including the implications of these developments on treatment strategies and the potential benefits and challenges of broader use in patients.

Panelists discuss their approach to biomarker testing in advanced endometrial cancer, including the timing and types of testing performed, the specific biomarkers assessed (such as mismatch repair/microsatellite instability, POLE, and TP53), and how these results inform treatment decisions.

Panelists discuss the integration of tisotumab vedotin into ovarian cancer therapy, covering its role in treatment approaches, patient selection, adverse event management, clinical pearls, challenges in practice, and the implications of the drug’s payload on treatment efficacy.

Panelists discuss key findings from the KEYNOTE-A18 trial, which evaluated pembrolizumab in combination with chemoradiotherapy for high-risk locally advanced cervical cancer, highlighting the implications for treatment approaches in this patient population.

Panelists discuss recent data on various antibody-drug conjugates (ADCs) in ovarian cancer, including mirvetuximab soravtansine from trials like FORWARD II, MIRASOL, and PICCOLO; luveltamab tazevibulin and rinatabart sesutecan from STRO-002-GM1 and REFRαME-O1; and raludotatug deruxtecan from REJOICE-Ovarian01, highlighting the evolving role of these agents in the treatment landscape for ovarian cancer.

Panelists discuss the recent tumor-agnostic approval of trastuzumab deruxtecan (T-DXd) based on findings from the DESTINY-PanTumor02 trial, its potential impact on treating advanced ovarian cancer given HER2 data, and how T-DXd may fit into the current treatment algorithm for ovarian cancer.

Panelists discuss strategies to address PARP inhibitor (PARPi) resistance in ovarian cancer, including emerging combinations like gotistobart + pembrolizumab from the PRESERVE-004 trial, insights from the SOPRANO trial on managing oligometastases or oligoprogression, and approaches to mitigate or manage common adverse events associated with PARPi maintenance therapy.

Panelists discuss how emerging maintenance strategies for advanced/metastatic disease increasingly focus on novel combination approaches, including immunotherapy combinations with PARP inhibitors (rucaparib + nivolumab), anti-angiogenic agents (atezolizumab + bevacizumab), and dual targeted therapy (olaparib + cediranib), with ongoing evaluation of optimal patient selection and sequencing in the treatment paradigm.

Panelists explore emerging combination therapies in maintenance treatment for advanced ovarian cancer, including rucaparib + nivolumab; atezolizumab + bevacizumab; and olaparib + cediranib, also discussing how these strategies fit into the current treatment paradigm and in which patient populations they may be considered.

Panelists discuss optimal durations for PARP inhibitor maintenance therapy in ovarian cancer, exploring how long patients are typically kept on PARPi in both first-line and second-line maintenance settings.

Panelists discuss frontline maintenance therapies for advanced ovarian cancer, focusing on the impact of BRCA and HRD statuses on treatment selection and the choice between combination therapy (PARPi + bev) and monotherapy.

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.