乌鸦传媒

The management of advanced endometrial cancer has seen significant advancements in recent years, with several studies demonstrating the benefits of incorporating checkpoint inhibitors into standard chemotherapy regimens. However, the applicability of these findings to the adjuvant setting remained unclear.

A recent study in the sought to address this knowledge gap by evaluating the addition of pembrolizumab to adjuvant chemotherapy, with or without radiotherapy, in patients with newly diagnosed, high-risk endometrial cancer. The protocol-prespecified subgroup analysis focused on the cohort with mismatch repair-deficient (dMMR) tumors.

The study enrolled a diverse population, including patients with stage I/II non-endometrioid tumors with myometrial invasion, stage I/II tumors of any histology with known aberrant p53 expression or mutation and myometrial invasion, as well as stage III/IV tumors of any histology.

The interim analysis revealed that the addition of pembrolizumab to adjuvant chemotherapy did not improve disease-free survival (DFS) in the overall study population. However, in the dMMR subgroup, the combination therapy demonstrated a clinically meaningful improvement in DFS compared with chemotherapy alone, with 2-year DFS rates of 92.4% and 80.2%, respectively.

Importantly, the benefit of pembrolizumab plus chemotherapy in the dMMR subgroup was consistent across various clinical and pathological factors, such as stage and histology. The safety profile was manageable, and patient-reported outcomes were similar between the two groups.

These findings suggest that the addition of pembrolizumab to standard adjuvant treatment may be particularly beneficial for patients with dMMR endometrial cancer, a subgroup with an inflamed tumor phenotype and poorer prognosis with conventional therapy alone. Further long-term follow-up is ongoing to fully evaluate the durability of these outcomes.

Ongoing trials are also exploring the potential of pembrolizumab as a single-agent therapy in the first-line setting for dMMR advanced/recurrent endometrial cancer, as well as in combination with radiotherapy for high-intermediate risk, dMMR, endometrioid endometrial cancer. These investigations may help refine the optimal integration of immunotherapy in the management of this disease.

Veena John, MD, is system head in Gynecologic Medical Oncology at Northwell Cancer Institute and associate professor at Zucker School of Medicine at Hofstra/Northwell Zuckerberg Cancer Center in Lake Success, New York.

Read the study here and an interview about it here.