Mayo Clinic, Jacksonville, FL, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Breast Cancer Res Treat. 2022 Jul;194(1):1-11. doi: 10.1007/s10549-021-06469-0. Epub 2022 May 19.
Human epidermal growth factor receptor 2 (HER2)-targeted therapies improve survival for patients with HER2-positive breast cancer but carry risks of hematologic, cardiopulmonary, gastro-hepatobiliary, and other adverse events (AEs). In this review, we describe published AE incidences for HER2-targeted therapies for metastatic breast cancer (mBC).
We searched PubMed and Embase to identify studies on HER2-targeted therapies in HER2-positive mBC, reporting on AEs of special interest, and published between January 1, 2009, and February 6, 2020. Treatment regimens were categorized into mutually exclusive therapy-based categories, with primary therapy determined by worldwide approval date.
One hundred and fifty-three included articles assessed a combined 29,238 patients treated with the following therapy-based regimens: trastuzumab or biosimilars (78 studies), lapatinib (40), T-DM1 (ado-trastuzumab emtansine) (20), pertuzumab (14), neratinib (8), MM-302 (1), T-DXd (2), tucatinib (3), and pyrotinib (3). While direct comparisons of AE incidence are not warranted owing to study heterogeneity, proportions of patients experiencing any Grade 3 + AE ranged across therapy-based regimens from 39.4% (lapatinib) to 66.3% (neratinib). The most common hematologic AE of special interest, of any grade and regardless of causality, was leukopenia/white blood cells decreased [21.4% (T-DXd)-46.2% (pyrotinib)]. Cardiopulmonary AEs of special interest included interstitial lung disease [2.7% (trastuzumab)-5.2% (T-DXd)], pneumonitis [0.2% (lapatinib)-7.4% (trastuzumab)], and decreased ejection fraction [1% (T-DXd)-13.6% (trastuzumab)]. Gastro-hepatobiliary AEs of special interest included nausea [33.9% (trastuzumab)-78.3% (T-DXd)], vomiting [19.2% (T-DM1)-48.2% (T-DXd)], diarrhea [19.6% (T-DM1)-96.9% (pyrotinib)], and hepatotoxicity [5.9% (lapatinib)-53.6% (T-DM1)].
Differing AE profiles for anti-HER2 therapies should be considered when assessing benefit-risk profile for treatment options.
人表皮生长因子受体 2（HER2）靶向治疗可提高 HER2 阳性乳腺癌患者的生存率，但存在血液学、心肺、胃肠-肝胆等不良事件（AE）风险。本综述描述了用于转移性乳腺癌（mBC）的 HER2 靶向治疗的已发表 AE 发生率。
我们检索了 PubMed 和 Embase，以确定 2009 年 1 月 1 日至 2020 年 2 月 6 日期间发表的关于 HER2 阳性 mBC 中 HER2 靶向治疗的具有特殊关注的 AE 的研究报告。治疗方案分为相互排斥的基于治疗的类别，主要治疗方案根据全球批准日期确定。
153 篇纳入的文章评估了 29238 例接受以下基于治疗方案治疗的患者：曲妥珠单抗或生物类似药（78 项研究）、拉帕替尼（40 项）、T-DM1（ado-trastuzumab emtansine）（20 项）、帕妥珠单抗（14 项）、奈拉替尼（8 项）、MM-302（1 项）、T-DXd（2 项）、图卡替尼（3 项）和吡咯替尼（3 项）。由于研究异质性，不保证对 AE 发生率进行直接比较，但基于治疗方案的患者发生任何 3 级及以上 AE 的比例从 39.4%（拉帕替尼）到 66.3%（奈拉替尼）不等。最常见的血液学特殊关注 AE，无论严重程度和因果关系如何，均为白细胞减少/白细胞减少症[21.4%（T-DXd）-46.2%（吡咯替尼）]。特殊关注的心肺 AE 包括间质性肺病[2.7%（曲妥珠单抗）-5.2%（T-DXd）]、肺炎[0.2%（拉帕替尼）-7.4%（曲妥珠单抗）]和射血分数降低[1%（T-DXd）-13.6%（曲妥珠单抗）]。特殊关注的胃肠-肝胆 AE 包括恶心[33.9%（曲妥珠单抗）-78.3%（T-DXd）]、呕吐[19.2%（T-DM1）-48.2%（T-DXd）]、腹泻[19.6%（T-DM1）-96.9%（吡咯替尼）]和肝毒性[5.9%（拉帕替尼）-53.6%（T-DM1）]。
在评估治疗选择的获益-风险特征时，应考虑抗 HER2 治疗的不同 AE 谱。
