Treatment of Unresectable or Recurrent Endometrial Carcinoma with Mismatch Repair Deficient (MMRd) Tumour

This protocol covers the first-line management of patients with unresectable stage III/IV or recurrent endometrial carcinoma whose tumour carries mismatch repair deficiency (MMRd), and who have not received prior chemotherapy outside the adjuvant setting.

Clinical Scenario

MMRd Tumour

Mismatch repair deficiency (MMRd) is the defining biomarker in this setting. Patients with MMRd tumours are candidates for an immune checkpoint inhibitor-based approach in combination with chemotherapy, followed by immune checkpoint inhibitor maintenance — a strategy supported by high-level evidence.

Tumour molecular profiling, including MMRd testing and, where applicable, HER2 status, is integral to guiding treatment selection in this population.

Treatment Approach (Partial Overview)

The protocol includes platinum-based systemic therapy as a component of management. Additional options — informed by individual tumour characteristics — may be relevant. Specific drug selection, sequencing, and eligibility criteria are set out in the full structured protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/S1470-2045(25)00167-6

Patients with MMRd tumours should be offered an immune checkpoint inhibitor (eg, dostarlimab, durvalumab, or pembrolizumab) in combination with carboplatin–paclitaxel chemotherapy, followed by immune checkpoint inhibitors as maintenance therapy (I, A).
Patients who have received immune checkpoint inhibitors as part of first-line therapy should be considered for systemic therapy with a platinum combination, doxorubicin, weekly paclitaxel, or endocrine therapy (IV, B).
For patients with HER2 overexpressing tumours, HER2 targeting strategies could be considered (II, B and III, B; appendix pp 17, 33, 34).

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