ADC联合PD-1抑制剂对比GC方案在膀胱癌新辅助治疗中的疗效及安全性研究

Efficacy and safety of ADC combined with PD-1 inhibitors versus GC regimen in neoadjuvant therapy for bladder cancer

摘要

目的 分析真实世界中抗体偶联药物（antibody–drug conjugates，ADC）联合程序性死亡受体1（programmed cell death 1，PD-1）抑制剂在膀胱癌新辅助治疗中的疗效和安全性。 方法 回顾性纳入2017年8月至2023年12月于重庆医科大学附属第一医院接受ADC联合PD-1抑制剂和吉西他滨/顺铂（Gemcitabine/Cisplatin，GC）方案新辅助治疗的29例膀胱癌患者，分为 A 组（维迪西妥单抗联合替雷利珠单抗）和B组（吉西他滨联合顺铂），对比分析 2 组患者的病理完全缓解率（pathological complete response，pCR）和病理降期率，同时评估用药期间患者所发生的不良事件（adverse events，AEs）。 结果 A组共纳入17例患者，其中13例行膀胱根治切除术，4例选择保膀胱手术，B组共纳入12例患者，均行膀胱根治切除术。A组pCR为41.2%，B组的pCR为25.0%，P=0.449；A组的病理降期率为58.8%，B组的病理降期率为50.0%，P=0.716。A组中常见的AEs包括肝功能异常10例（58.8%），外周感觉神经功能减退8例（47.1%），贫血7例（41.2%）等，其中3～4级AEs共6例（35.3%）。B组中常见的 AEs包括贫血9例（75%），中性粒细胞减少8例（66.7%），恶心8例（66.7%）等，其中3～4级AEs共3例（25.0%）。 结论 在膀胱癌新辅助治疗中，ADC（维迪西妥单抗）联合PD-1抑制剂（替雷利珠单抗）较传统的GC方案具有更高的pCR和病理降期率，同时安全性可控，在人类表皮生长因子2阴性的患者中也有较好的疗效。

Abstract

Objective To analyze the efficacy and safety of antibody-drug conjugates（ADCs） combined with programmed cell death 1（PD-1） inhibitors in neoadjuvant therapy for bladder cancer in real-world settings. Methods A retrospective study was conducted on 29 patients with bladder cancer who received ADC combined with PD-1 inhibitors or gemcitabine/cisplatin as neoadjuvant therapy at The First Affiliated Hospital of Chongqing Medical University between August 2017 and December 2023. The patients were divided into Group A（disitamab vedotin combined with atezolizumab） and Group B（gemcitabine combined with cisplatin）. The pathological complete response rate and pathological downstaging rate were compared between the two groups. The adverse events that occurred during treatment were evaluated. Results Group A included 17 patients，among whom 13 patients underwent radical cystectomy，and 4 patients opted for bladder-preserving surgery. Group B included 12 patients，all of whom underwent radical cystectomy. The pathological complete response rate was 41.2% in Group A and 25.0% in Group B（P=0.449）. The pathological downstaging rate was 58.8% in Group A and 50.0% in Group B（P=0.716）. Common adverse events in Group A included abnormal liver function（10 cases，58.8%），peripheral sensory neuropathy（8 cases，47.1%），and anemia（7 cases，41.2%），with 6 cases（35.3%） experiencing grade 3-4 AEs. In Group B，common adverse events included anemia（9 cases，75%），neutropenia（8 cases，66.7%），and nausea（8 cases，66.7%），with 3 cases（25.0%） experiencing grade 3-4 adverse events. Conclusion In neoadjuvant therapy for bladder cancer，ADC（disitamab vedotin） combined with PD-1 inhibitor（atezolizumab） has higher pathological complete response rate and pathological downstaging rate compared to the traditional gemcitabine/cisplatin regimen. Additionally，its safety profile is manageable，and it demonstrates good efficacy in human epidermal growth receptor 2-negative patients.

关键词

抗体偶联药物 / 膀胱癌 / 新辅助治疗 / 不良事件

Key words

antibody-drug conjugate / bladder cancer / neoadjuvant therapy / adverse event