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三阴性乳腺癌的免疫治疗:如何增强早期疾病中实验药物的病理反应?

Immunotherapy for triple negative breast cancer: How can pathologic responses to experimental drugs in early-stage disease be enhanced?

机构信息

Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy.

Department of Oncology and Haematology, University of Milan, Milan, Italy.

出版信息

Expert Opin Investig Drugs. 2022 Aug;31(8):855-874. doi: 10.1080/13543784.2022.2095260. Epub 2022 Jul 6.

Abstract

INTRODUCTION

The treatment landscape of early triple-negative breast cancer (TNBC) has recently expanded after the Food and Drug Administration (FDA) approval of pembrolizumab in combination with neoadjuvant chemotherapy. The addition of this immune checkpoint inhibitor (ICI) has shown significantly increased pathological complete response (pCR) rate and event-free survival (EFS) in the KEYNOTE-522 phase III trial. Several additional studies are ongoing with the goal of further improving the outcomes and achieving an optimal integration of ICIs in the treatment of TNBC.

AREAS COVERED

The article examines pCR and survival rates in TNBC. It appraises clinical trials investigating neoadjuvant ICIs for TNBC and the improvement of pCR rates (biomarker-driven escalation of treatment, optimization of chemotherapy backbone, and addition of locoregional treatments or innovative agents). Insights into the role of pCR as a surrogate endpoint and the possibility of enhancing pCR rates for women affected by early TNBC are offered.

EXPERT OPINION

The pharmacopoeia of early TNBC is growing and becoming more heterogeneous with the advent of ICIs; to enhance the clinical benefit of patients, it is necessary to develop response endpoints that consider the mechanism of action of experimental drugs, to optimize patient selection through validated biomarkers, and to compare the most promising treatment strategies in randomized clinical trials.

摘要

简介

在食品和药物管理局(FDA)批准帕博利珠单抗联合新辅助化疗后,早期三阴性乳腺癌(TNBC)的治疗格局最近得到了扩展。在 KEYNOTE-522 三期试验中,这种免疫检查点抑制剂(ICI)的加入显著提高了病理完全缓解(pCR)率和无事件生存(EFS)率。目前正在进行几项额外的研究,目的是进一步改善结果,并实现 ICIs 在 TNBC 治疗中的最佳整合。

涵盖领域

本文检查了 TNBC 的 pCR 和生存率。它评估了新辅助 ICIs 治疗 TNBC 的临床试验,以及 pCR 率的提高(基于生物标志物的治疗升级、化疗骨干的优化,以及局部区域治疗或创新药物的添加)。探讨了 pCR 作为替代终点的作用,以及提高早期 TNBC 女性 pCR 率的可能性。

专家意见

随着 ICIs 的出现,早期 TNBC 的药物学正在发展并变得更加多样化;为了提高患者的临床获益,有必要开发考虑实验药物作用机制的反应终点,通过验证的生物标志物优化患者选择,并在随机临床试验中比较最有前途的治疗策略。

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