Leslie M. Randall, MD; Thomas C. Krivak, MD; Rebecca C. Arend, MD, MPH; Tara Berman, MD, MS; and Gottfried E. Konecny, MD, discuss how molecular testing and biomarker-driven treatment strategies are revolutionizing gynecologic oncology across ovarian, cervical, and endometrial cancers.
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 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 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 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 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 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 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 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 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 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 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 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 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 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.
