仑伐替尼联合PD-1抑制剂作为不可切除胆管癌患者的一线治疗：一项单臂、开放标签的II期研究。

Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study.

作者信息

Zhang Qiyi, Liu Xingyu, Wei Shumei, Zhang Lufei, Tian Yang, Gao Zhenzhen, Jin Ming, Yan Sheng

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.

Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.

出版信息

Front Oncol. 2021 Nov 24;11:751391. doi: 10.3389/fonc.2021.751391. eCollection 2021.

OBJECTIVE

We investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC).

METHODS

In this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; <60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers.

RESULTS

Among 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6-11.4) and the median OS was 17.7 months (95% CI: not estimable).

CONCLUSIONS

Lenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated.

CLINICAL TRIAL REGISTRATION

www.chictr.org.cn, ChiCTR2100044476.

目的

我们研究了乐伐替尼联合程序性细胞死亡蛋白1（PD-1）抑制剂作为初治不可切除胆管癌（BTC）一线治疗方案的疗效。

方法

在这项II期研究中，初治不可切除BTC的成年患者每日接受乐伐替尼治疗（体重≥60 kg，12 mg；<60 kg，8 mg），每3周接受一次PD-1抑制剂治疗（帕博利珠单抗/替雷利珠单抗/信迪利单抗/卡瑞利珠单抗200 mg或特瑞普利单抗240 mg）。主要终点为客观缓解率（ORR）和安全性。次要终点包括手术转化率、疾病控制率（DCR）、无事件生存期（EFS）、总生存期（OS）和肿瘤生物标志物。

结果

在38例入组患者中，ORR为42.1%，DCR为76.3%。13例（34.2%）患者实现降期并接受手术，其中6例（46.2%）在原发肿瘤中达到主要病理缓解（n = 2）或部分病理缓解（n = 4）。总体而言，84.2%的患者发生≥1次治疗相关不良事件（TRAE），34.2%的患者发生≥3级TRAE，未发生与治疗相关的死亡。中位随访13.7个月后，中位EFS为8.0个月（95%CI：4.6 - 11.4），中位OS为17.7个月（95%CI：无法估计）。