Kim Mi-Hyun, Seong Hayoung, Kim Soo Han, Lee Min Ki, Kim Insu, Hong Kyung Soo, Ahn June Hong, Eom Jung Seop
Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
Department of Internal Medicine, Pusan National University Hospital, Busan, Korea.
Korean J Intern Med. 2025 Jul;40(4):626-633. doi: 10.3904/kjim.2024.269. Epub 2025 Jul 1.
BACKGROUND/AIMS: This study investigated the efficacy and safety of first-line afatinib treatment in older patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).
This retrospective, multicenter, observational cohort study included 103 patients aged ≥ 75 years who were treated with first-line afatinib for EGFR-mutated NSCLC. The primary outcome was time-on-treatment (TOT).
The median TOT of patients was 13.6 months (95% confidence interval 11.0-16.2). Ninety-two patients (89.3%) required dose modification. Dose reduction was significantly more frequent in the 40 mg starting dose group than in the 30 mg group (93.1% vs. 68.8%, p = 0.004). The most common grade 3 or worse adverse events (AEs) were diarrhea (n = 16, 54%), acneiform rash (n = 4, 14.3%), and stomatitis (n = 4, 14.3%). Grade 3 or worse AEs led to dose modification in 23 of 28 patients (82.1%) and permanent discontinuation of therapy in five of 28 patients (17.9%). On disease progression, tissue re-biopsy was performed in 18 of 74 patients (24.3%). Thirty-four patients (45.9%) received subsequent chemotherapy; of these, most patients (n = 21, 61.8%) received pemetrexed monotherapy.
This study demonstrated the efficacy of first-line afatinib treatment for EGFR-mutant NSCLC in older patients. However, despite similar safety profiles and frequencies of AEs reported in previous studies, the frequency of dose modifications was higher in this population. A 30 mg starting dose of afatinib and a predefined dose adjustment may be suitable strategies for this population. Post-tyrosine kinase inhibitor management, such as tissue re-biopsy and platinum-based chemotherapy, tended to be underprescribed in this age group.
背景/目的：本研究调查了一线阿法替尼治疗老年表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的疗效和安全性。
这项回顾性、多中心、观察性队列研究纳入了103例年龄≥75岁、接受一线阿法替尼治疗EGFR突变NSCLC的患者。主要结局是治疗时间（TOT）。
患者的中位TOT为13.6个月（95%置信区间11.0 - 16.2）。92例患者（89.3%）需要调整剂量。起始剂量40mg组的剂量降低频率显著高于30mg组（93.1%对68.8%，p = 0.004）。最常见的3级或更严重不良事件（AE）为腹泻（n = 16，54%）、痤疮样皮疹（n = 4，14.3%）和口腔炎（n = 4，14.3%）。3级或更严重AE导致28例患者中的23例（82.1%）调整剂量，28例患者中的5例（17.9%）永久停药。疾病进展时，74例患者中的18例（24.3%）进行了组织重新活检。34例患者（45.9%）接受了后续化疗；其中，大多数患者（n = 21，61.8%）接受培美曲塞单药治疗。
本研究证明了一线阿法替尼治疗老年EGFR突变NSCLC的疗效。然而，尽管本研究报告的安全性特征和AE发生率与既往研究相似，但该人群中剂量调整的频率更高。阿法替尼30mg起始剂量和预定义的剂量调整可能是适合该人群的策略。在这个年龄组中，酪氨酸激酶抑制剂治疗后的管理，如组织重新活检和铂类化疗，往往未得到充分应用。
