Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
Department of Pathology, The First People's Hospital of Yancheng City, Yancheng, China.
Mol Med. 2023 Oct 6;29(1):134. doi: 10.1186/s10020-023-00736-0.
Positive human epidermal growth factor receptor 2 (HER2) expression is associated with an increased risk of metastases especially those to the brain in patients with advanced breast cancer (BC). Neratinib as a tyrosine kinase inhibitor can prevent the transduction of HER1, HER2 and HER4 signaling pathways thus playing an anticancer effect. Moreover, neratinib has a certain efficacy to reverse drug resistance in patients with BC with previous HER2 monoclonal antibody or targeted drug resistance. Neratinib, as monotherapy and in combination with other therapies, has been tested in the neoadjuvant, adjuvant, and metastatic settings. Neratinib with high anticancer activity is indicated for the prolonged adjuvant treatment of HER2-positive early BC, or in combination with other drugs including trastuzumab, capecitabine, and paclitaxel for the treatment of advanced HER2-positive BC especially cancers with central nervous system (CNS) metastasis to reduce the risk of BC recurrence. This article reviewed the pharmacological profiles, efficacy, safety, tolerability, and current clinical trials pertaining to neratinib, with a particular focus on the use of neratinib in patients with metastatic breast cancer (MBC) involving the CNS. We further discussed the use of neratinib for HER2-negative and HER2-mutant breast cancers, and mechanisms of resistance to neratinib. The current evidence suggests that neratinib has promising efficacy in patients with BC which is at least non-inferior compared to previous therapeutic regimens. The most common AE was diarrhea, and the incidence, severity and duration of neratinib-related grade 3 diarrhea can be reduced with loperamide. Of note, neratinib has the potential to effectively control and prevent brain metastasis in patients with advanced BC, providing a therapeutic strategy for HER2-positive BC.
阳性人类表皮生长因子受体 2（HER2）表达与晚期乳腺癌（BC）患者转移，尤其是脑转移的风险增加有关。作为一种酪氨酸激酶抑制剂，奈拉替尼可以阻止 HER1、HER2 和 HER4 信号通路的转导，从而发挥抗癌作用。此外，奈拉替尼对先前 HER2 单克隆抗体或靶向药物耐药的 BC 患者具有一定的耐药逆转作用。奈拉替尼作为单药治疗和联合其他疗法，已在新辅助、辅助和转移性环境中进行了测试。奈拉替尼具有较高的抗癌活性，用于延长 HER2 阳性早期 BC 的辅助治疗，或与其他药物联合使用，包括曲妥珠单抗、卡培他滨和紫杉醇，用于治疗晚期 HER2 阳性 BC，特别是伴有中枢神经系统（CNS）转移的癌症，以降低 BC 复发的风险。本文综述了奈拉替尼的药理学特征、疗效、安全性、耐受性和目前的临床试验，特别关注奈拉替尼在涉及中枢神经系统的转移性乳腺癌（MBC）患者中的应用。我们进一步讨论了奈拉替尼在 HER2 阴性和 HER2 突变型乳腺癌中的应用以及对奈拉替尼的耐药机制。目前的证据表明，奈拉替尼在 BC 患者中具有有前景的疗效，至少与之前的治疗方案相比非劣效。最常见的 AE 是腹泻，洛哌丁胺可降低奈拉替尼相关 3 级腹泻的发生率、严重程度和持续时间。值得注意的是，奈拉替尼有可能有效控制和预防晚期 BC 患者的脑转移，为 HER2 阳性 BC 提供了一种治疗策略。
