Abstract：
BACKGROUND: The Proactive Molecular Risk Classifier for Endometrial Cancer has identified four risk groups for the prognosis of endometrial cancer. Lenvatinib plus pembrolizumab was recently approved as a second-line treatment for unresectable endometrial cancer, but reports in clinical practice are lacking. The relationship between the efficacy of lenvatinib/pembrolizumab and Proactive Molecular Risk Classifier for Endometrial Cancer classification is unclear.
METHODS: This single-centre retrospective study included patients who underwent lenvatinib/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital\'s ethics committee (approval number: MH2022-093).
RESULTS: This study enrolled 20 patients, who underwent a median follow-up of 17.8 months (95% confidence interval: 16.6-18.9). The best overall response rate was 60.0% (36.1-80.9), and the median progression-free survival was 11.6 months (2.9-20.3). The median progression-free survival in the p53 abnormal group (n = 9) was 3.4 months (3.0-3.8); however, progression-free survival did not reach the median (P < 0.001) in the mismatch repair-deficient/no specific molecular profile group (n = 11). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred.
CONCLUSIONS: The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib/pembrolizumab.
METHODS: This single-centre retrospective study included patients who underwent lenvatinib/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital\'s ethics committee (approval number: MH2022-093).
RESULTS: This study enrolled 20 patients, who underwent a median follow-up of 17.8 months (95% confidence interval: 16.6-18.9). The best overall response rate was 60.0% (36.1-80.9), and the median progression-free survival was 11.6 months (2.9-20.3). The median progression-free survival in the p53 abnormal group (n = 9) was 3.4 months (3.0-3.8); however, progression-free survival did not reach the median (P < 0.001) in the mismatch repair-deficient/no specific molecular profile group (n = 11). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred.
CONCLUSIONS: The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib/pembrolizumab.
摘要：
背景：子宫内膜癌的前瞻性分子风险分类法已经确定了子宫内膜癌预后的四个风险组。Lenvatinib联合pembrolizumab最近被批准作为二线治疗不可切除的子宫内膜癌，但是临床实践中缺乏报道。lenvatinib/pembrolizumab与前反应性分子风险分类法对子宫内膜癌分类的疗效之间的关系尚不清楚。
方法：这项单中心回顾性研究包括2022年1月至2023年3月在岩手医科大学医院接受lenvatinib/pembrolizumab治疗的患者。收集治疗前从患者获得的福尔马林固定石蜡包埋标本，并将其分类为错配修复缺陷，使用免疫组织化学的p53异常和没有特定的分子谱亚型。响应率，使用电子病历评估无进展生存期和不良事件.该研究获得了医院伦理委员会的批准（批准号：MH2022-093）。
结果：这项研究招募了20名患者，中位随访时间为17.8个月(95%置信区间:16.6-18.9).最佳总有效率为60.0%（36.1-80.9），中位无进展生存期为11.6个月(2.9-20.3).p53异常组（n=9）的中位无进展生存期为3.4个月（3.0-3.8）；然而，在错配修复缺陷/无特定分子谱组(n=11)中,无进展生存期未达到中位数(P<0.001).4/20（25.0%）患者发生症状性免疫相关不良事件（甲状腺功能减退除外），在所有病例中均观察到部分反应。无治疗相关死亡发生。
结论：子宫内膜癌前兆分子风险分类法中的p53abn组即使在接受乐伐替尼/派姆单抗治疗后预后也较差。
方法：这项单中心回顾性研究包括2022年1月至2023年3月在岩手医科大学医院接受lenvatinib/pembrolizumab治疗的患者。收集治疗前从患者获得的福尔马林固定石蜡包埋标本，并将其分类为错配修复缺陷，使用免疫组织化学的p53异常和没有特定的分子谱亚型。响应率，使用电子病历评估无进展生存期和不良事件.该研究获得了医院伦理委员会的批准（批准号：MH2022-093）。
结果：这项研究招募了20名患者，中位随访时间为17.8个月(95%置信区间:16.6-18.9).最佳总有效率为60.0%（36.1-80.9），中位无进展生存期为11.6个月(2.9-20.3).p53异常组（n=9）的中位无进展生存期为3.4个月（3.0-3.8）；然而，在错配修复缺陷/无特定分子谱组(n=11)中,无进展生存期未达到中位数(P<0.001).4/20（25.0%）患者发生症状性免疫相关不良事件（甲状腺功能减退除外），在所有病例中均观察到部分反应。无治疗相关死亡发生。
结论：子宫内膜癌前兆分子风险分类法中的p53abn组即使在接受乐伐替尼/派姆单抗治疗后预后也较差。
