{"title":"CDK4/6 inhibitors in the treatment of metastatic breast cancer: Focus on toxicity and safety","authors":"Demi Wekking, Matteo Lambertini, Mariele Dessì, Nerina Denaro, Fabio Bardanzellu, Ornella Garrone, Mario Scartozzi, Cinzia Solinas","doi":"10.1053/j.seminoncol.2024.01.002","DOIUrl":null,"url":null,"abstract":"<p>The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). When combined with an aromatase inhibitor or fulvestrant, these agents have been approved as first-line therapy in the metastatic setting. Abemaciclib has also gained FDA approval for patients with HR-positive, HER2-negative, node-positive, early BC at high risk of recurrence. Moreover, ribociclib has recently improved disease-free survival in patients with stage II or III HR+/HER2-negative early BC. CDK4/6 inhibitors have favorable safety profiles. However, the available agents have different toxicity profiles that must be clearly discussed with the patients for optimal clinical decisions. This manuscript aims to review CDK4/6 inhibitor-related treatment-associated adverse events, identify risk factors for intolerable adverse events, and assess their safety in special patient populations such as the elderly and those with renal insufficiency. Enhanced knowledge and understanding of CDK4/6 inhibitor-related toxicities can improve treatment strategies and ultimately enhance patient care.</p>","PeriodicalId":21750,"journal":{"name":"Seminars in oncology","volume":"13 1","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Seminars in oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1053/j.seminoncol.2024.01.002","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). When combined with an aromatase inhibitor or fulvestrant, these agents have been approved as first-line therapy in the metastatic setting. Abemaciclib has also gained FDA approval for patients with HR-positive, HER2-negative, node-positive, early BC at high risk of recurrence. Moreover, ribociclib has recently improved disease-free survival in patients with stage II or III HR+/HER2-negative early BC. CDK4/6 inhibitors have favorable safety profiles. However, the available agents have different toxicity profiles that must be clearly discussed with the patients for optimal clinical decisions. This manuscript aims to review CDK4/6 inhibitor-related treatment-associated adverse events, identify risk factors for intolerable adverse events, and assess their safety in special patient populations such as the elderly and those with renal insufficiency. Enhanced knowledge and understanding of CDK4/6 inhibitor-related toxicities can improve treatment strategies and ultimately enhance patient care.
口服细胞周期蛋白依赖性激酶4和6(CDK4/6)抑制剂(包括palbociclib、ribociclib和abemaciclib)的开发彻底改变了激素受体阳性(HR+)和人表皮生长因子受体2(HER2)阴性转移性乳腺癌(BC)患者的治疗格局。当与芳香化酶抑制剂或氟维司群联合使用时,这些药物已被批准作为转移性乳腺癌的一线疗法。Abemaciclib 也获得了 FDA 批准,用于治疗 HR 阳性、HER2 阴性、结节阳性、复发风险高的早期 BC 患者。此外,ribociclib最近也改善了II期或III期HR+/HER2阴性早期BC患者的无病生存期。CDK4/6 抑制剂具有良好的安全性。然而,现有的药物具有不同的毒性特征,必须与患者进行明确讨论,以做出最佳临床决策。本手稿旨在回顾CDK4/6抑制剂治疗相关不良事件,识别不可耐受不良事件的风险因素,并评估其在老年人和肾功能不全患者等特殊患者群体中的安全性。加强对CDK4/6抑制剂相关毒性的认识和理解可以改善治疗策略,最终提高患者护理水平。
期刊介绍:
Seminars in Oncology brings you current, authoritative, and practical reviews of developments in the etiology, diagnosis and management of cancer. Each issue examines topics of clinical importance, with an emphasis on providing both the basic knowledge needed to better understand a topic as well as evidence-based opinions from leaders in the field. Seminars in Oncology also seeks to be a venue for sharing a diversity of opinions including those that might be considered "outside the box". We welcome a healthy and respectful exchange of opinions and urge you to approach us with your insights as well as suggestions of topics that you deem worthy of coverage. By helping the reader understand the basic biology and the therapy of cancer as they learn the nuances from experts, all in a journal that encourages the exchange of ideas we aim to help move the treatment of cancer forward.