Promising response to neoadjuvant pembrolizumab and low-dose chemotherapy in advanced endometrial cancer: A preliminary report

OBJECTIVE: Recent trials demonstrated improved outcomes with immunotherapy-chemotherapy combinations in advanced endometrial cancer (EC) with mismatch repair deficiency (dMMR). We evaluated clinical characteristics, treatment responses, and safety of patients with advanced EC receiving neoadjuvant immunotherapy with low-dose chemotherapy (NIC). STUDY DESIGN: ) and carboplatin (AUC 2) on days 8 and 15 every 21 days, for one to four cycles prior to surgery. RESULTS: The median age was 64.5 years (range: 45-78). Molecular studies revealed dMMR tumors in four patients, including two also with p53-abnormal features (p53abn); missmatch repair proficient (pMMR) and p53abn in three patients; and nonspecific molecular profile in one patient. Four patients achieved complete radiologic response by RECIST v1.1 criteria, whereas four demonstrated partial responses with tumor regression ranging from 41% to 92%. Pathological evaluation documented complete response in four patients with diverse histologic subtypes: undifferentiated/dedifferentiated (n = 1), serous (n = 1), grade 3 endometrioid (n = 1), and clear cell carcinoma (n = 1). Complete responses occurred in both serous and clear cell carcinomas despite typically unfavorable p53abn molecular profiles. At median follow-up of 3.6 months after complete therapy, one patient progressed. All patients completed treatment without grade ≥3 adverse events per CTCAE criteria. CONCLUSION: Neoadjuvant pembrolizumab with low-dose chemotherapy demonstrated promising efficacy and acceptable safety in advanced EC, with favorable outcomes in high-grade malignancies regardless of molecular subtype. These findings warrant further investigation in selected patients.