仑伐替尼联合程序性死亡蛋白-1 抑制剂用于一线全身治疗后难治性晚期胆道癌的真实世界回顾性研究：中国的研究。

Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China.

机构信息

Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Affiliated to Naval Medical University, Shanghai, China.

Department of Biliary Tract Surgery III, Eastern Hepatobiliary Surgery Hospital, Affiliated to Naval Medical University, Shanghai, China.

出版信息

Front Immunol. 2022 Jul 27;13:946861. doi: 10.3389/fimmu.2022.946861. eCollection 2022.

BACKGROUND

Currently, no second-line systemic treatment regimen has been recommended in advanced biliary tract cancer (BTC). Cumulative clinical evidence showed that systemic treatment with tyrosine kinase inhibitors (TKIs) in combination with immunotherapy may shed light on the dim clinical outcome in advanced BTC.

OBJECTIVE

The aim of this study is to evaluate the anticancer efficacy of lenvatinib plus programmed cell death protein-1 (PD-1) antibody in patients with BTC who progressed after first-line cisplatin/gemcitabine (CisGem) chemotherapy.

METHODS

Patients with advanced BTCs who progressed after CisGem were recruited. A combination regimen of lenvatinib (8/12 mg daily) plus PD-1 antibody (200/240 mg injection every 3 weeks) was prescribed. Clinicopathological information and therapeutic outcome, including tumor subtypes, biomarkers, treatment duration, adverse events (AE), progression-free survival (PFS), and overall survival (OS), were recorded and estimated.

RESULTS

A total of 351 patients with BTCs were reviewed and 74 were recruited eventually: 35 had intrahepatic cholangiocarcinoma (47.3%), 4 had extrahepatic cholangiocarcinoma (5.4%), and 35 had gallbladder cancer (47.3%). The median administered cycles of PD-1 antibody were 6.43 (95% CI: 5.83-7.04) cycles, and the median duration of lenvatinib medication was 21.0 weeks (95% CI: 18.04-23.93). Twenty-eight patients (37.83%) experienced detectable objective response per RECIST1.1 within a median follow-up duration of 15.0 months. The objective response rate (ORR) was 20.27% (95% CI: 10.89%-29.65%), and the disease control rate (DCR) was 71.62% (95% CI: 61.11%-82.14%). The median PFS and OS were 4.0 months (95% CI: 3.5-5.0) and 9.50 months (95% CI: 9.0-11.0), respectively. Seventy-three patients (98.64%) reported AEs and 39 (52.70%) experienced ≥grade 3 AEs. In subgroup analyses, tumoral PD-L1 expression ≥50% and tumor mutation burden (TMB) ≥2.5 Muts/Mb were associated with prolonged PFS.

CONCLUSION

Lenvatinib plus PD-1 antibody treatment shows an active trend towards improving survival in patients with advanced BTCs after failure with CisGem chemotherapy. The treatment-related AEs are worthy of attention and are manageable.

背景

目前，晚期胆道癌（BTC）尚无二线系统治疗方案。累积的临床证据表明，酪氨酸激酶抑制剂（TKI）联合免疫治疗的全身治疗可能为晚期 BTC 的暗淡临床结局带来曙光。

目的

本研究旨在评估仑伐替尼联合程序性死亡蛋白-1（PD-1）抗体在一线顺铂/吉西他滨（CisGem）化疗后进展的 BTC 患者中的抗癌疗效。

方法

招募了进展期 BTC 患者，这些患者在 CisGem 后进展。处方仑伐替尼（8/12mg 每日）联合 PD-1 抗体（200/240mg 每 3 周注射）的联合治疗方案。记录和估计了包括肿瘤亚型、生物标志物、治疗持续时间、不良事件（AE）、无进展生存期（PFS）和总生存期（OS）在内的临床病理信息和治疗结果。

结果

共回顾了 351 例 BTC 患者，最终纳入 74 例：35 例为肝内胆管癌（47.3%），4 例为肝外胆管癌（5.4%），35 例为胆囊癌（47.3%）。PD-1 抗体的中位给药周期为 6.43（95%CI：5.83-7.04）个周期，仑伐替尼用药的中位持续时间为 21.0 周（95%CI：18.04-23.93）。在中位随访时间为 15.0 个月时，根据 RECIST1.1 标准，有 28 名患者（37.83%）检测到客观缓解。客观缓解率（ORR）为 20.27%（95%CI：10.89%-29.65%），疾病控制率（DCR）为 71.62%（95%CI：61.11%-82.14%）。中位 PFS 和 OS 分别为 4.0 个月（95%CI：3.5-5.0）和 9.50 个月（95%CI：9.0-11.0）。73 名患者（98.64%）报告了 AE，39 名患者（52.70%）发生了≥3 级 AE。在亚组分析中，肿瘤 PD-L1 表达≥50%和肿瘤突变负荷（TMB）≥2.5 Muts/Mb 与 PFS延长相关。