First-line · Advanced / Recurrent · Non-MMRd
Treatment of Unresectable Stage III/IV or Recurrent Endometrial Carcinoma with Non-MMRd Tumour and Rapidly Growing or Symptomatic Disease
This protocol applies to patients with unresectable stage III or IV endometrial carcinoma, or with recurrent disease, whose tumours are non-mismatch-repair deficient (non-MMRd) and who present with rapidly growing or symptomatic disease. These patients have received no prior chemotherapy outside of the adjuvant setting.
Clinical Scenario
Non-MMRd endometrial tumours in the unresectable or recurrent setting with rapid progression or significant symptom burden require prompt systemic intervention. The absence of mismatch-repair deficiency defines the therapeutic context for this population and shapes the choice between available strategies.
Treatment Approach
Systemic chemotherapy is the recommended backbone of treatment for this population. Depending on specific tumour characteristics, protocol-defined alternatives incorporating immune checkpoint inhibitors — alone or combined with additional targeted agents — may also be considered.
Full regimen details, sequencing, applicable alternatives, and criteria for each option are in the complete protocol below.
References
- Patients with non-MMRd tumours with rapidly growing or symptomatic disease should be offered carboplatin–paclitaxel chemotherapy (I, A).
- Immune checkpoint inhibitors plus chemotherapy, followed by immune checkpoint inhibitors as maintenance therapy (eg, dostarlimab or pembrolizumab), or immune checkpoint inhibitors plus chemotherapy, followed by immune checkpoint inhibitors and PARP inhibitors as maintenance therapy (eg, durvalumab and olaparib), can be considered (I, B).
- If immune checkpoint inhibitors (with or without PARP inhibitors) are contraindicated for patients with a HER2 3+ (strong overexpression) tumour, carboplatin–paclitaxel plus trastuzumab can be considered (II, B).
DOI: 10.1016/S1470-2045(25)00167-6
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