A phase II study to evaluate the safety and efficacy of anlotinib combined with toripalimab for advanced biliary tract cancer

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology Pub Date : 2024-01-12 DOI:10.1002/cti2.1483

Mingzhen Zhou, Yuncheng Jin, Sihui Zhu, Chen Xu, Lin Li, Baorui Liu, Jie Shen

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Abstract

Objectives

To assess the safety and efficacy of anlotinib (a multi-targeted tyrosine kinase inhibitor) combined with toripalimab (a PD-1 monoclonal antibody) in the treatment of unresectable biliary tract cancer (BTC).

Methods

In this prospective, single-arm, single-centre exploratory clinical study, patients with locally progressed or metastatic BTC were included. Patients were treated with anlotinib (12 mg, PO, QD, for 2 weeks and then stopped for a week, 21 days for a cycle) and toripalimab (240 mg, IV, Q3W). The primary endpoint of the study was the objective response rate (ORR), as defined in RECIST version 1.1 criteria.

Results

In this study, 15 BTC patients who met the criteria were enrolled. The ORR was 26.7%, the median progression-free survival (mPFS) was 8.6 months (95% CI: 2.1–15.2), the median overall survival (mOS) was 14.53 months (95% CI: 0.8–28.2) and the disease control rate (DCR) was 87.6%. A patient with hilar cholangiocarcinoma was successfully converted after three cycles of treatment and underwent surgical resection. Furthermore, patient gene sequencing revealed that STK11 was mutated more frequently in patients with poor outcomes. In addition, patients with a CD8/Foxp3 ratio > 3 had a longer survival than those with a CD8/Foxp3 ratio ≤ 3 (P = 0.0397).

Conclusions

In patients with advanced BTC, the combination of anlotinib and toripalimab demonstrated remarkable anti-tumor potential, with increased objective response rates (ORR), longer overall survival (OS) and progression-free survival (PFS). Moreover, STK11 and CD8/Foxp3 may be as biomarkers that can predict the effectiveness of targeted therapy in combination with immunotherapy.

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评估安罗替尼联合托利帕单抗治疗晚期胆道癌的安全性和有效性的II期研究

目的评估安罗替尼（一种多靶点酪氨酸激酶抑制剂）联合托利帕利单抗（一种PD-1单克隆抗体）治疗无法切除的胆道癌（BTC）的安全性和有效性。方法在这项前瞻性、单臂、单中心探索性临床研究中，纳入了局部进展或转移性 BTC 患者。患者接受安罗替尼治疗（12 毫克，口服，每天一次，持续 2 周，然后停药一周，21 天为一个周期）和托利帕单抗治疗（240 毫克，静脉注射，每天三次）。研究的主要终点是客观反应率（ORR），其定义符合 RECIST 1.1 版标准。结果本研究共招募了 15 名符合标准的 BTC 患者。ORR为26.7%，中位无进展生存期（mPFS）为8.6个月（95% CI：2.1-15.2），中位总生存期（mOS）为14.53个月（95% CI：0.8-28.2），疾病控制率（DCR）为87.6%。一名患有肝门部胆管癌的患者在接受了三个周期的治疗后成功转为肝门部胆管癌，并接受了手术切除。此外，患者基因测序结果显示，STK11在预后较差的患者中发生突变的频率较高。此外，CD8/Foxp3比值为> 3的患者比CD8/Foxp3比值≤3的患者生存期更长（P = 0.0397）。结论在晚期 BTC 患者中，安罗替尼和托利帕利单抗的联合用药显示出显著的抗肿瘤潜力，客观反应率（ORR）提高，总生存期（OS）和无进展生存期（PFS）延长。此外，STK11和CD8/Foxp3可能是预测靶向疗法与免疫疗法联合治疗效果的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical & Translational Immunology Medicine-Immunology and Allergy

CiteScore

12.00

自引率

1.70%

发文量

审稿时长

13 weeks

期刊介绍： Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.