1 University of Houston College of Pharmacy, Houston, TX, USA.
2 Lester and Sue Smith Breast Center, Houston, TX, USA.
Ann Pharmacother. 2019 Jun;53(6):612-620. doi: 10.1177/1060028018824088. Epub 2019 Jan 4.
To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib in human epidermal growth factor receptor (HER2)+ breast cancer (BC).
A PubMed search was performed using the term neratinib between September 12, 2018, and November 21, 2018. References of published articles and reviews were also assessed for additional information.
English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib were evaluated.
Neratinib, an irreversible inhibitor of HER1, HER2, and HER4, is Food and Drug Administration approved for the extended adjuvant treatment of stage I-III HER2+ BC to follow trastuzumab-based therapy. A phase III study has demonstrated statistically significant improvement in 5-year disease-free survival rate (90.2 vs 87.7; hazard ratio = 0.73, 95% CI = 0.57-0.92, P = 0.0083). Its most common adverse effect is diarrhea, observed in more than 90% of patients. The incidence of grade 3/4 diarrhea (~40%) is reduced by half with loperamide prophylaxis, which is recommended for the first 8 weeks of neratinib therapy. Other common adverse reactions are nausea and fatigue. The patients need to be monitored for liver function tests and drug interactions with acid-reducing agents, CYP3A4 inhibitors/inducers, and P-glycoprotein substrates with narrow therapeutic window. Relevance to Patient Care and Clinical Practice: American Society of Clinical Oncology and National Comprehensive Cancer Network clinical guidelines suggest the use of neratinib for extended adjuvant therapy following 1-year trastuzumab in stage I to III HER2+ BC. Diarrhea remains a clinically significant but manageable adverse event.
Neratinib significantly improves treatment outcomes and has manageable toxicity in stage I to III HER2+ BC patients.
综述人表皮生长因子受体（HER2）+乳腺癌（BC）中奈拉替尼的化学、药理学、药代动力学、安全性和疗效。
2018 年 9 月 12 日至 2018 年 11 月 21 日，使用术语“neratinib”在 PubMed 上进行了搜索。还评估了已发表文章和综述的参考文献，以获取更多信息。
评估了奈拉替尼的化学、药理学、药代动力学、安全性和疗效的临床前和临床英语研究。
奈拉替尼是一种不可逆的 HER1、HER2 和 HER4 抑制剂，已获美国食品和药物管理局批准，用于曲妥珠单抗为基础的治疗后，扩展治疗 I-III 期 HER2+BC。一项 III 期研究表明，5 年无病生存率（90.2%比 87.7%；风险比=0.73，95%CI=0.57-0.92，P=0.0083）有统计学显著改善。其最常见的不良反应是腹泻，超过 90%的患者出现。洛哌丁胺预防可使腹泻发生率（约 40%）降低一半，因此建议在奈拉替尼治疗的前 8 周使用。其他常见的不良反应是恶心和疲劳。需要监测肝功能检查以及与抑酸剂、CYP3A4 抑制剂/诱导剂和具有狭窄治疗窗的 P-糖蛋白底物的药物相互作用。
美国临床肿瘤学会和国家综合癌症网络临床指南建议，在 I 至 III 期 HER2+BC 患者中，曲妥珠单抗治疗 1 年后，使用奈拉替尼进行扩展辅助治疗。腹泻仍然是一个具有临床意义但可管理的不良事件。
奈拉替尼显著改善了 I 至 III 期 HER2+BC 患者的治疗结果，且毒性可管理。
