Optimizing Management Strategies for Advanced Endometrial Cancer Progression After IO-Chemo

Summary for Physicians: Treating Patients With Advanced EC Who Progress After IO-Chemotherapy

For patients with advanced EC who progress after IO therapy combined with chemotherapy, the treatment strategy typically involves considering several options based on individual patient factors, tumor characteristics, and prior treatment response.

1. Assessing Tumor Characteristics and Biomarkers:

• Biomarker testing remains essential to guide decision-making. Key biomarkers such as mismatch repair deficiency status (dMMR), microsatellite instability (MSI), tumor mutational burden, and others should be reassessed to guide further treatment strategies.

• For patients with dMMR or MSI-high (H) tumors, further IO options or clinical trial enrollment may be considered, as they might still benefit from additional immunotherapy.

1. Alternative Immunotherapy Approaches:

• If a patient did not respond to initial IO therapy (eg, pembrolizumab or nivolumab), combination therapies such as lenvatinib (an antiangiogenic agent) and pembrolizumab are becoming an important option, particularly for dMMR or MSI-H tumors.

• Second-line immunotherapy (such as additional PD-1/PD-L1 inhibitors) could be considered, especially if the patient has not previously received certain IO regimens.

1. Chemotherapy and Other Targeted Therapies:

• For patients who do not respond to IO therapies, switching to traditional chemotherapy (such as carboplatin and paclitaxel) or other targeted therapies such as PI3K/ Akt/mTOR inhibitors may be appropriate.

• Clinical trials focusing on novel therapies such as antibody-drug conjugates, PARP inhibitors, or new IO combinations should be explored if available.

1. Personalized Treatment Decisions:

• Treatment decisions should be individualized, considering the patient’s response to previous therapies, performance status, comorbidities, and preferences.

• Multidisciplinary collaboration is key in these complex cases, with input from pathologists, geneticists, and supportive care teams to ensure the best possible outcomes.

In summary, treating patients with advanced EC who progress after IO-chemotherapy requires a multifaceted approach that includes reassessing tumor characteristics, considering alternative immunotherapy or targeted therapies, and exploring clinical trials. Personalizing treatment plans based on biomarker status and previous responses remains crucial in optimizing care.