Wang Shao-Jing, Chen Hsin-Hua, Sun Lou, Shih Yu-Hsiang, Lu Ting-Fang, Chen Yen-Fu, Fan Chun-Ting, Hsu Shih-Tien, Liu Chin-Ku, Hwang Sheau-Feng, Lu Chien-Hsing
Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
J Clin Med. 2024 Sep 24;13(19):5670. doi: 10.3390/jcm13195670.
: The treatment-free interval is a significant predictor of worse prognosis and poor response rates of the second-line treatment in patients with carboplatin and paclitaxel (PT)-pretreated, advanced, or recurrent endometrial cancer (EC). Whether lenvatinib plus pembrolizumab still confers a survival benefit compared with doxorubicin in patients with platinum-free intervals of <6 months remains unclear. : This multi-institutional retrospective analysis was performed using de-identified electronic health records from the TriNetX Research Network. Patients with advanced or recurrent ECs who received lenvatinib plus pembrolizumab or doxorubicin within six months of first-line PT were identified. A 1:1 propensity score matching (PSM) was conducted to control for potential confounding variables. Overall survival (OS) and adverse event profile were the primary and secondary outcomes. : Between January 2018 and February 2024, 130 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab and 122 patients who received doxorubicin at a platinum-free interval of <6 months were identified across 31 healthcare organizations. In the balanced cohort following PSM with 117 patients in each group, treatment with lenvatinib plus pembrolizumab was associated with improved OS compared with treatment with doxorubicin (12.8 vs. 8.2 months, = 0.012, hazard ratio: 0.65, 95% confidence interval: 0.46-0.91). Regarding adverse event analysis, a higher incidence of hypothyroidism and proteinuria was observed with lenvatinib plus pembrolizumab, and more hematological toxicities were observed with doxorubicin. : in patients with treatment-free intervals of <6 months, lenvatinib plus pembrolizumab still confers improved survival compared with doxorubicin in PT-treated, advanced, or recurrent ECs.
无治疗间隔时间是接受卡铂和紫杉醇（PT）预处理的晚期或复发性子宫内膜癌（EC）患者预后较差和二线治疗缓解率低的重要预测指标。对于无铂间隔时间<6个月的患者，与多柔比星相比，乐伐替尼联合帕博利珠单抗是否仍能带来生存获益尚不清楚。
本多机构回顾性分析使用了来自TriNetX研究网络的去识别电子健康记录。确定了在一线PT治疗后6个月内接受乐伐替尼联合帕博利珠单抗或多柔比星治疗的晚期或复发性EC患者。进行了1:1倾向评分匹配（PSM）以控制潜在的混杂变量。总生存期（OS）和不良事件情况是主要和次要结局。
在2018年1月至2024年2月期间，在31个医疗机构中确定了130例接受PT治疗的晚期或复发性EC患者接受了乐伐替尼联合帕博利珠单抗治疗，122例患者在无铂间隔时间<6个月时接受了多柔比星治疗。在每组117例患者的PSM平衡队列中，与多柔比星治疗相比，乐伐替尼联合帕博利珠单抗治疗与改善的OS相关（12.8个月对8.2个月，P = 0.012，风险比：0.65，95%置信区间：0.46 - 0.91）。关于不良事件分析，乐伐替尼联合帕博利珠单抗组观察到甲状腺功能减退和蛋白尿的发生率较高，多柔比星组观察到更多血液学毒性。
在无治疗间隔时间<6个月的患者中，与多柔比星相比，乐伐替尼联合帕博利珠单抗在PT治疗的晚期或复发性EC患者中仍能改善生存。
