Background: The treatment options for HER2-negative metastatic breast cancer include targeted therapies, cytotoxic chemotherapies, and immunotherapy. However, limited specificity and inevitable resistance highlight the need for novel agents. Antibody–drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), represent a breakthrough by selectively delivering cytotoxic agents to tumor cells, potentially improving the therapeutic index. Despite demonstrated efficacy, ADCs present toxicity profiles similar to conventional chemotherapy, alongside unique adverse events. In clinical practice, oncologists may face scenarios where both T-DXd and SG are treatment options in HER2-negative mBC. To enable shared decision-making, it is crucial to present a comprehensive overview that includes both efficacy data and detailed toxicity profiles. Our objective was to provide a pooled and informative synthesis of toxicities from pivotal studies, including graphical representations, to support informed, patient-centered medical decisions. Methods: We reviewed safety data from phase 3 clinical trials in HER2-negative mBC: DESTINY-Breast04/DESTINY-Breast06 for T-DXd and ASCENT/TROPICS-02 for SG. Adverse event (AE) profiles, including frequency and severity, were extracted, and weighted means were calculated. Emerging ADCs such as datopotamab deruxtecan and patritumab deruxtecan were considered to contextualize future therapeutic decisions. Results: Tables, bar plots and radar plots were generated. T-DXd demonstrated high rates of nausea (69.2%), fatigue (47.2%), and neutropenia (35.6%), with 52.7% experiencing grade ≥ 3 AEs. Notably, pneumonitis occurred in 10.7%, with grade ≥ 3 in 2.6%. SG showed a distinct AE profile, with higher incidences of neutropenia (67.1%), with grade ≥ 3 in 51.3%, and diarrhea (60.8%). Conclusions: The choice between ADCs in HER2-negative metastatic BC when both T-DXd and SG are treatment options should consider toxicity profiles to optimize patient-centered treatment strategies. Tailoring ADC selection based on individual tolerance and preferences is critical for shared decision-making, and future research should focus on assessing the utility and acceptability of such clinical tools to guide treatment selection.
背景：HER2阴性转移性乳腺癌的治疗方案包括靶向治疗、细胞毒性化疗和免疫治疗。然而，有限的靶向性和不可避免的耐药性凸显了对新型药物的需求。抗体偶联药物（ADCs），如德曲妥珠单抗（T-DXd）和戈沙妥珠单抗（SG），通过选择性将细胞毒性药物递送至肿瘤细胞，代表了治疗突破，有望提高治疗指数。尽管已证实其疗效，ADCs的毒性特征与传统化疗相似，同时伴有独特的不良事件。在临床实践中，肿瘤科医生可能面临T-DXd和SG均为HER2阴性转移性乳腺癌治疗选择的场景。为促进共同决策，提供包含疗效数据和详细毒性特征的全面概述至关重要。我们的目标是通过汇总关键研究中的毒性数据（包括图表展示），提供信息丰富的综合分析，以支持以患者为中心的知情医疗决策。 方法：我们回顾了HER2阴性转移性乳腺癌的3期临床试验安全性数据：T-DXd的DESTINY-Breast04/DESTINY-Breast06研究和SG的ASCENT/TROPICS-02研究。提取了不良事件（AE）特征（包括发生频率和严重程度），并计算加权平均值。同时考虑了德达托妥单抗和帕妥珠单抗等新兴ADCs，以展望未来治疗决策的背景。 结果：研究制作了表格、条形图和雷达图。T-DXd表现出较高的恶心（69.2%）、疲劳（47.2%）和中性粒细胞减少（35.6%）发生率，52.7%的患者出现≥3级AE。值得注意的是，肺炎发生率为10.7%，其中≥3级占2.6%。SG显示出不同的AE特征，中性粒细胞减少发生率更高（67.1%，其中≥3级占51.3%），腹泻发生率为60.8%。 结论：当T-DXd和SG均为治疗选择时，HER2阴性转移性乳腺癌的ADC选择应考虑毒性特征，以优化以患者为中心的治疗策略。根据个体耐受性和偏好定制ADC选择对共同决策至关重要，未来研究应侧重于评估此类临床工具在指导治疗选择中的实用性和可接受性。
肿瘤(癌症)患者之家