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Opinion|Videos|May 13, 2026

Biomarker-Driven Treatment Decisions and Managing Progression After Frontline Immunotherapy

Author(s)Robert M. Wenham, MD, Premal H. Thaker, MD, MS, Tiffany Redfern, MD, FACOG

Upfront biomarker testing reshapes endometrial cancer care, guiding targeted and immune therapy—and exposing gaps in second-line options.

Episodes in this series

4 experts are featured in this series.

EP. 1 The Endometrial Cancer Treatment Landscape

4 experts are featured in this series.

EP. 2 RUBY Trial Design, Efficacy, and Real-World Evidence for Dostarlimab

4 experts are featured in this series.

EP. 3 Four-Year Follow-Up Outcomes in dMMR Endometrial Cancer Presented at SGO 2026

4 experts are featured in this series.

EP. 4 Comparing Approved Checkpoint Inhibitor Regimens and Optimal Treatment Duration

4 experts are featured in this series.

EP. 5 Biomarker-Driven Treatment Decisions and Managing Progression After Frontline Immunotherapy

4 experts are featured in this series.

EP. 6 Emerging Clinical Trials and Future Therapeutic Strategies in Recurrent Endometrial Cancer

The panel transitions to biomarker testing and treatment sequencing in patients who progress after frontline immunotherapy. Dr. Redfern describes her standardized approach to upfront immunohistochemistry testing across all endometrial cancer patients regardless of histology, emphasizing the value of consistency to avoid testing gaps and treatment delays. Dr. Konecny outlines the evolution from a histology-based framework to a molecularly driven approach encompassing mismatch repair status, p53 mutation, HER2 amplification, and hormone receptor expression. The panel then addresses the unmet need for patients who progress on frontline checkpoint inhibitor therapy—particularly those with mismatch repair–proficient disease—and discusses off-label use of lenvatinib plus pembrolizumab in this setting. Dr. Thaker notes that available approved options remain limited for checkpoint inhibitor–exposed patients, underscoring the urgency of clinical trial enrollment and the potential of emerging agents including antibody-drug conjugates.

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