Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study.
Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study.
复制标题
DOI：
10.1038/s41392-023-01317-7
复制
发表时间：
2023-03-17
影响因子：
39.3
通讯作者：
Zhou, Jian
中科院分区：
文献类型：
--
作者：
Shi, Guo-Ming;Huang, Xiao-Yong;Wu, Dong;Sun, Hui-Chuan;Liang, Fei;Ji, Yuan;Chen, Yi;Yang, Guo-Huan;Lu, Jia-Cheng;Meng, Xian-Long;Wang, Xin-Ying;Sun, Lei;Ge, Ning-Ling;Huang, Xiao-Wu;Qiu, Shuang-Jian;Yang, Xin-Rong;Gao, Qiang;He, Yi-Feng;Xu, Yang;Sun, Jian;Ren, Zheng-Gang;Fan, Jia;Zhou, Jian
晚期肝内胆管细胞癌（ICC）预后不良。在此，我们报告了联合使用托立普利单抗、乐伐替尼和吉西他滨加奥沙利铂（GEMOX）作为晚期ICC一线治疗的疗效和安全性。30例经病理学证实的晚期ICC患者在第1天和第8天接受吉西他滨（1 g/m2）静脉给药，奥沙利铂（85 mg/m2）Q3 W，共沿着6个周期，同时接受托里普利单抗（240 mg）Q3 W静脉给药和乐伐替尼（8 mg）口服给药，每日1次，持续1年。采用免疫组织化学和全外显子组测序（WES）分析法研究石蜡包埋组织中程序性死亡配体1（PD-L1）的表达和遗传状态。主要终点为客观缓解率（ORR）。次要结局包括安全性、总生存期（OS）、无进展生存期（PFS）、疾病控制率（DCR）和缓解持续时间（DoR）。截至2022年7月1日，中位随访时间为23.5个月，ORR为80%。23例患者获得部分缓解，1例获得完全缓解。DNA损伤反应（DDR）相关基因突变的患者（21/30）显示出较高的ORR，而肿瘤面积阳性≥1（PD-L1染色）的患者（14/30）显示出较高的ORR趋势，但无显著差异。中位OS、PFS和DoR分别为22.5、10.2和11.0个月。DCR为93.3%。此外，56.7%的患者发生了可管理的≥3级不良事件（AE），通常为中性粒细胞减少症（40.0%）和白细胞减少症（23.3%）。总之，toripalimab + lenvatinib和GEMOX是治疗晚期ICC的有前景的一线方案。国家药品监督管理局批准了一项III期、多中心、双盲、随机研究，以验证我们的研究结果（NMPA，编号2021 LP 01825）。临床试验注册：NCT 03951597。
Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m2) on Days 1 and 8 and oxaliplatin (85 mg/m2) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC. A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825). Trial registration Clinical trials: NCT03951597.
登录
查看更多内容
DOI：
10.1038/s41571-018-0114-z
发表时间：
2019-03
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Pilié PG;Tang C;Mills GB;Yap TA
通讯作者：
Yap TA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
45.3
作者：
Taylor, Matthew H.;Lee, Chung-Han;Motzer, Robert J.
通讯作者：
Motzer, Robert J.
影响因子：
3.9
作者：
Liu, Ze-Long;Liu, Xin;Kuang, Ming
通讯作者：
Kuang, Ming
DOI：
10.1056/evidoa2200015
发表时间：
2022-08-01
期刊：
NEJM evidence
影响因子：
--
作者：
Oh, Do-Youn;Ruth He, Aiwu;Valle, Juan W
通讯作者：
Valle, Juan W