Neoadjuvant GOLP in Resectable High-Risk Intrahepatic Cholangiocarcinoma.

The GOLP regimen (gemcitabine-oxaliplatin, lenvatinib, and an anti-programmed death 1 antibody) has shown promising efficacy with a manageable safety profile in advanced intrahepatic cholangiocarcinoma and biliary tract cancer.

GOLP方案（吉西他滨-奥沙利铂，仑伐替尼和抗程序性死亡1抗体）在晚期肝内胆管癌和胆道癌中显示出有前景的疗效，并具有可控的安全性。

Methods

In a phase 2-3 trial, we randomly assigned, in a 1:1 ratio, patients with resectable high-risk intrahepatic cholangiocarcinoma to the neoadjuvant group (intravenous gemcitabine-oxaliplatin plus toripalimab every 3 weeks for three cycles and oral lenvatinib once daily for 9 weeks, followed by curative resection) or the control group (curative resection and no neoadjuvant treatment).

在一项2-3期临床试验中，我们按照1:1的比例，随机将可切除的高风险肝内胆管癌患者分配到新辅助治疗组（每3周静脉注射吉西他滨-奥沙利铂加托利帕利单抗，共三个周期，以及每天口服仑伐替尼9周，随后进行根治性切除术）或对照组（仅进行根治性切除术，不进行新辅助治疗）。

All patients received adjuvant capecitabine for eight cycles after surgery.

所有患者在手术后均接受八个周期的辅助化疗药物卡培他滨。

The primary end point was event-free survival. Secondary end points included overall survivaland safety.

主要终点是无事件生存。次要终点包括总生存和安全性。

Results

A total of 178 patients underwent randomization (88 patients to the neoadjuvant group and 90 to the control group).

共有178名患者进行了随机分组（新辅助治疗组88名患者，对照组90名患者）。

At the interim analysis at a median follow-up of 16.9 months, the median event-free survival was significantly longer in the neoadjuvant group (18.0 months; 95% confidence interval[CI], 13.8 to 27.6) than in the control group (8.7 months; 95% CI, 7.2 to 12.4) (P<0.001).

在中位随访16.9个月的中期分析中，新辅助治疗组的中位无事件生存期显著长于对照组（新辅助治疗组：18.0个月；95%置信区间[CI]，13.8至27.6个月；对照组：8.7个月；95% CI，7.2至12.4个月）（P<0.001）。

Overall survivalat 24 months was 79% (95% CI, 70 to 90) in the neoadjuvant group and 61% (95% CI, 50 to 75) in the control group (hazard ratiofor death, 0.43; 95% CI, 0.23 to 0.79; P = 0.005, which did not meet the significance criterion [two-sided alpha, 0.0019]).

24个月的总生存率在新辅助治疗组为79%（95%置信区间[CI]，70至90），对照组为61%（95% CI，50至75）（死亡风险比为0.43；95% CI，0.23至0.79；P = 0.005，未达到显著性标准[双侧α，0.0019]）。

Across all treatment phases, adverse events occurred in 97% of the patients in the neoadjuvant group and in 70% of those in the control group.

在所有治疗阶段中，新辅助治疗组中有97%的患者出现了不良事件，而对照组中有70%的患者出现了不良事件。

During the neoadjuvant phase, adverse events of grade 3 or higher occurred in 28% of the patients, and treatment-related adverse events of grade 3 or higher in 26%.

在新辅助治疗阶段，3级或更高级别的不良事件发生在28%的患者中，与治疗相关的3级或更高级别的不良事件发生在26%的患者中。

No treatment-related adverse eventled to death.

没有治疗相关的不良事件导致死亡。

Conclusions

Neoadjuvant GOLP led to significantly longer event-free survival than control therapy, with mainly low-grade adverse events, among patients with resectable high-risk intrahepatic cholangiocarcinoma.

新辅助GOLP治疗在可切除的高风险肝内胆管癌患者中，与对照治疗相比，显著延长了无事件生存期，且主要为低级别不良事件。

(Funded by the Clinical Research Plan of Shanghai Hospital Development Center and others; ZSAB-neoGOLP ClinicalTrials.gov number, NCT04669496.).

(由上海市医院发展中心临床研究计划等资助; ZSAB-neoGOLP ClinicalTrials.gov编号, NCT04669496。)