Pembrolizumab for Endometrial Cancer: The Evidence

Endometrial carcinoma is the most common gynaecological cancer in the UK. While many cases are diagnosed at an early stage where surgery is curative, patients with advanced or recurrent disease have historically had limited treatment options. Pembrolizumab - both alone and in combination - has changed the treatment landscape significantly.

MSI-H endometrial cancer: KEYNOTE-158

A significant proportion of endometrial cancers - particularly endometrioid subtypes - exhibit microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) status. These tumours have a very high mutational load, making them highly immunogenic and particularly responsive to checkpoint inhibitor therapy. KEYNOTE-158 evaluated pembrolizumab monotherapy in MSI-H solid tumours across multiple cancer types, including endometrial cancer. Response rates in MSI-H endometrial cancer were substantially higher than historical rates with chemotherapy, and some responses were highly durable.

KEYNOTE-775: Pembrolizumab plus lenvatinib

For patients without MSI-H tumours - the majority of patients with advanced endometrial cancer - pembrolizumab monotherapy has more limited activity. KEYNOTE-775 addressed this population by combining pembrolizumab with lenvatinib, a tyrosine kinase inhibitor. The combination produced significantly improved progression-free and overall survival compared to standard chemotherapy in previously treated patients, regardless of MSI status. This approval was particularly significant for the larger group of patients with microsatellite-stable (MSS) endometrial cancer who do not benefit from immunotherapy alone.

Pembrolizumab in the first-line setting

More recently, pembrolizumab added to platinum-based chemotherapy has been evaluated in the first-line advanced endometrial cancer setting, with results demonstrating improved outcomes, particularly in patients with dMMR/MSI-H tumours. The evolving treatment landscape means that MSI/MMR testing is now standard for newly diagnosed advanced endometrial cancer.

What this means for patients

If you have advanced or recurrent endometrial cancer, knowing your MMR/MSI status is essential - it directly determines which pembrolizumab-based approach is most likely to benefit you. An oncologist experienced in gynaecological cancers will be best placed to interpret your results and advise on the most appropriate treatment sequence.