The efficacy and safety of lenvatinib plus pembrolizumab therapy in patients with uterine carcinosarcoma.

Lenvatinib plus pembrolizumab (LP) therapy is currently used in patients with advanced or recurrent endometrial cancer. However, patients with uterine carcinosarcoma (UCS) were not included in the KEYNOTE-775, and the efficacy of LP therapy for patients with UCS in clinical practice remains unclear. We administered LP therapy to five patients with UCS. We aimed to report our clinical experience with LP therapy in these patients and investigate the genomic characteristics of those who responded to LP therapy. We retrospectively reviewed patients with UCS (n = 5) who underwent LP therapy at our hospital from January 2019 to December 2023. Efficacy was assessed using the response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Safety was evaluated in terms of adverse events. The median age was 65 (55-78) years, and the mismatch repair status was proficient in all of the patients. One patient had stage II disease, and four had stage III. The median number of LP therapy courses was 8 (1-35). The overall response rate was 40%. None of the patients experienced adverse events that were grade 3 or higher. The median follow-up duration was 9 (1-26) months, median progression-free survival was 9.1 (0.16 to NA) months, and median overall survival was 10.2 (1.41 to NA) months. LP therapy may be effective for patients with UCS. As this report was based on a limited number of patients, more cases are required to investigate the efficacy of LP therapy in patients with UCS.

Unveiling pembrolizumab effectiveness in diverse subtypes of MSI-high endometrial cancers.

OBJECTIVE: The efficacy of pembrolizumab in patients with microsatellite instability (MSI)-high cancers has been reported; however, the differences in efficacy according to the subtypes of MSI-high endometrial cancers (ECs) remain unclear. MSI-high ECs are classified into at least 3 groups based on their molecular characteristics: MLH1 hypermethylated, Lynch-like syndrome (LLS)-associated, and Lynch syndrome (LS)-associated cancers. This study aimed to investigate whether the efficacy of pembrolizumab differs among these 3 groups, and if so, whether EPM2AIP1 immunohistochemistry (IHC), which correlates with MLH1 promoter methylation, can be used to rule out MLH1 methylation cases. METHODS: This study included 12 patients with MSI-high EC who received pembrolizumab treatment. Patients were categorized into 3 groups based on MLH1 methylation analysis and the Amsterdam Criteria: MLH1 hypermethylated (sporadic [SP]), LLS-associated, and LS-associated. Patients' medical records were retrospectively reviewed, and the efficacy of treatment was evaluated based on the response rate using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: The overall response rate was 75% (3/4) in the SP group, while it was 100% including one complete response patient in the LLS-associated and the LS-associated group, respectively. The sensitivity and positive predictive value of EPM2AIP1 IHC for MLH1 methylation were 100% and 66.7%, respectively. CONCLUSION: Pembrolizumab may be more effective in LLS and LS-associated groups. EPM2AIP1 IHC was less predictive than MLH1 methylation analysis; however, it may be useful for ruling out MLH1 methylation cases due to its high sensitivity. Further studies are needed to determine whether EPM2AIP1 IHC can predict pembrolizumab efficacy.

Benign metastasising leiomyoma with endometrial carcinoma, with a differential diagnosis of metastatic lung cancer.

Benign metastasising leiomyoma (BML) is a rare disease in which histologically benign uterine fibroids spread throughout the body. It is thought to originate from the hematogenous metastasis of myoma cells following myomectomy. To date, BML has been noted in patients with respiratory symptoms, even during regular checkups. There are few case reports of co-occurrence with gynaecological cancer. We report the case of a suspected stage IVb carcinoma based on preoperative examination for endometrial cancer, that indicated lung metastasis. However, postoperative pathology revealed a grade 1, pT1a pN0 tumour. We suspected BML based on the discrepant findings and history of myomectomy, and this was confirmed by lung biopsy. In metastatic lesions of a carcinoma patient with a history of myomectomy, the co-occurrence of BML should be considered when there is discrepancy between the preoperative suspected stage and postoperative pathology.