Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis

IF 9.6 1区医学 Q1 ONCOLOGY

Cancer treatment reviews Pub Date : 2025-01-01 DOI:10.1016/j.ctrv.2024.102865

Francesco Schettini , Sabrina Nucera , Tomás Pascual , Olga Martínez-Sáez , Rodrigo Sánchez-Bayona , Benedetta Conte , Giuseppe Buono , Matteo Lambertini , Kevin Punie , Juan Miguel Cejalvo , Grazia Arpino , Paolo Vigneri , Daniele Generali , Eva Ciruelos , Javier Cortés , Alessandra Gennari , Montserrat Muñoz , Maria J. Vidal Losada , Sara M Tolaney , Aleix Prat , Guillermo Villacampa

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引用次数: 0

Abstract

Introduction

Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).

Methods

We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd. Hazard ratios (HRs) with 95 % confidence intervals (CI) were calculated for PFS/OS. P-score was used for treatment ranking.

Results

Three RCTs (956 patients) were included in the primary analysis and 5 (1,445) in the exploratory NMA with Dato-DXd. In HR+/HER2-low, T-DXd showed no significant difference in PFS and OS when compared to SG. Similarly, in TN/HER2-low, PFS and OS did not differ significantly between the two ADCs. The P-score analysis favored T-DXd over SG in HR+/HER2-low in PFS (0.90 vs. 0.60) and OS (0.89 vs. 0.60). SG was favored over T-DXd in OS in TN/HER2-low (0.80 vs. 0.69). Similar results were obtained for HR+ MBC when including Dato-Dxd, which showed the worst performance, while T-DXd was the only ADC significantly outperforming CT in OS. The ADCs showed significantly better PFS and OS than CT in HR+/HER2-low and TN/HER2-low (all p < 0.001). SG had higher rates of neutropenia, diarrhea and alopecia vs. T-DXd, which showed more thrombocytopenia, fatigue and nausea. Pneumonitis and cardiotoxicity were typically T-DXd-related, and T-DXd showed more toxicity-related discontinuations.

Conclusions

Similar efficacy with T-DXd and SG in HER2-low MBC was observed, regardless of HR status. Safety profile, local drug-approval criteria and guidelines, patients’ preferences and overall quality of evidence should ultimately guide therapeutic decision-making. Dato-DXd role remains uncertain.

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抗体-药物偶联物在预处理her2低转移性乳腺癌中的疗效和安全性：系统综述和网络荟萃分析

抗体-药物偶联物（adc）曲妥珠单抗-德鲁西替康（T-DXd）和sacituzumab-govitecan （SG）在预处理激素受体阳性（HR+）和三阴性(TN)/ her2低转移性乳腺癌（MBC）中，比化疗（CT）提供了显著的无进展生存期（PFS）和总生存期（OS）改善。然而，两者之间没有直接的比较，也没有与最近的datopotamab-deruxtecan （Dato-DXd）进行比较。方法：通过网络荟萃分析（NMA）比较T-DXd和SG在CT预处理的HR+和TN/ her2低MBC中的疗效和安全性，并评估其相对于标准CT的益处，同时探讨与Dato-DXd的比较。计算PFS/OS的风险比（hr）和95%置信区间（CI）。采用P-score进行治疗排序。结果：3个随机对照试验（956例）被纳入初级分析，5个随机对照试验（1445例）被纳入探索性NMA与Dato-DXd。在HR+/HER2-low组，T-DXd组与SG组相比PFS和OS无显著差异。同样，在TN/ her2低的情况下，两种adc的PFS和OS无显著差异。p评分分析表明，在HR+/ her2低的PFS （0.90 vs 0.60）和OS （0.89 vs 0.60）中，T-DXd优于SG。在TN/ her2低的OS中，SG优于T-DXd （0.80 vs 0.69）。HR+ MBC在加入Dato-Dxd后也得到了类似的结果，Dato-Dxd表现最差，而T-DXd是OS中唯一表现明显优于CT的ADC。在HR+/ her2低和TN/ her2低的情况下，adc的PFS和OS明显优于CT（均为p）。结论：无论HR状态如何，在her2低的MBC中，T-DXd和SG的疗效相似。安全性概况、当地药物批准标准和指南、患者偏好和总体证据质量应最终指导治疗决策。Dato-DXd的作用仍然不确定。

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来源期刊

Cancer treatment reviews 医学-肿瘤学

CiteScore

21.40

自引率

0.80%

发文量

109

审稿时长

13 days

期刊介绍： Cancer Treatment Reviews Journal Overview: International journal focused on developments in cancer treatment research Publishes state-of-the-art, authoritative reviews to keep clinicians and researchers informed Regular Sections in Each Issue: Comments on Controversy Tumor Reviews Anti-tumor Treatments New Drugs Complications of Treatment General and Supportive Care Laboratory/Clinic Interface Submission and Editorial System: Online submission and editorial system for Cancer Treatment Reviews