Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Oncologist. 2018 Aug;23(8):891-899. doi: 10.1634/theoncologist.2017-0582. Epub 2018 Apr 12.
Dermatologic adverse events (dAEs) are common with the use of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. First- and second-generation agents (erlotinib, gefitinib, and afatinib) are frequently associated with acneiform rash, pruritus, xerosis, and paronychia; the incidence and characterization of these dAEs have been well described. However, there is evidence that the dAE profile is different with third-generation EGFR-TKIs. Herein, we describe the dAEs associated with third-generation EGFR-TKIs and our clinical experience with osimertinib, a third-generation EGFR-TKI approved by the U.S. Food and Drug Administration for the treatment of metastatic, T790M mutation-positive non-small cell lung cancer in patients whose disease has progressed on or after EGFR-TKI therapy. Case summaries of patients from two of our institutions who received osimertinib and were referred to a dermatologist for dAEs are also presented. Overall, the evidence suggests that osimertinib is associated with less severe and less frequent dAEs than first- and second-generation EGFR-TKIs and that therefore a different approach is warranted. Finally, we outline dAE management approaches for osimertinib in the context of those typically employed with first- and second-generation EGFR-TKIs.
Appropriate prevention and management of dermatologic adverse events (dAEs) associated with the use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) may help patients to continue therapy and lessen any negative impact on their quality of life. EGFR-TKIs are frequently associated with acneiform rash, pruritus, xerosis, and paronychia; however, dAEs associated with third-generation EGFR-TKIs are lower in frequency and severity. Before therapy, health care providers should discuss the potential osimertinib-associated dAEs and encourage patients to report their dAEs. Patients should also be educated on prophylactic measures to minimize the severity of dAEs and the importance of adherence to the treatment regimen.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗会引起常见的皮肤不良反应（dAEs）。第一代和第二代药物（厄洛替尼、吉非替尼和阿法替尼）常引起痤疮样皮疹、瘙痒、干燥和甲周炎；这些 dAEs 的发生率和特征已有详细描述。然而，有证据表明第三代 EGFR-TKIs 的 dAE 谱不同。在此，我们描述了第三代 EGFR-TKIs 相关的 dAEs 以及我们使用第三代 EGFR-TKI 奥希替尼的临床经验，该药获美国食品和药物管理局批准，用于治疗接受过 EGFR-TKI 治疗后疾病进展的、携带 T790M 突变的转移性非小细胞肺癌患者。我们还介绍了来自我们的两个机构的接受奥希替尼治疗并因 dAEs 而被转介至皮肤科医生的患者的病例总结。总的来说，证据表明奥希替尼相关的 dAEs 比第一代和第二代 EGFR-TKIs 更轻微且更不频繁，因此需要采取不同的方法。最后，我们概述了奥希替尼的 dAE 管理方法，这些方法与第一代和第二代 EGFR-TKIs 中常用的方法类似。
适当预防和管理表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）相关的皮肤不良反应（dAEs）可能有助于患者继续治疗并减轻其生活质量的负面影响。EGFR-TKIs 常引起痤疮样皮疹、瘙痒、干燥和甲周炎；然而，第三代 EGFR-TKIs 相关的 dAEs 频率和严重程度较低。在治疗前，医务人员应讨论奥希替尼相关的 dAEs，并鼓励患者报告其 dAEs。还应教育患者采取预防措施以最小化 dAEs 的严重程度，并强调坚持治疗方案的重要性。
