对于携带19外显子或21外显子突变的IV期肺腺癌患者，每日起始剂量30毫克阿法替尼的临床疗效可能不劣于每日40毫克阿法替尼。
The clinical efficacy of Afatinib 30 mg daily as starting dose may not be inferior to Afatinib 40 mg daily in patients with stage IV lung Adenocarcinoma harboring exon 19 or exon 21 mutations.
作者信息
Yang Chih-Jen, Tsai Ming-Ju, Hung Jen-Yu, Lee Mei-Hsuan, Tsai Ying-Ming, Tsai Yu-Chen, Hsu Jui-Feng, Liu Ta-Chih, Huang Ming-Shyan, Chong Inn-Wen
机构信息
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou First Road, Kaohsiung City, Taiwan.
出版信息
BMC Pharmacol Toxicol. 2017 Dec 13;18(1):82. doi: 10.1186/s40360-017-0190-1.
BACKGROUND
Afatinib is a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Compared to cytotoxic chemotherapy, afatinib has been shown to have better efficacy in the treatment of non-small cell lung cancer harboring EGFR mutations. However, 40 mg daily as the initial dose is often accompanied by serious adverse drug reactions (ADRs) and 28 to 53.3% of patients required a dose reduction. No previous study has compared the clinical efficacy and ADRs of different initial doses (40 mg vs. 30 mg daily) of afatinib in lung cancer treatment.
METHODS
Patients with stage IV lung adenocarcinoma diagnosed and treated in two Kaohsiung Medical University-affiliated hospitals in Taiwan between May 2014 and August 2016 were identified and followed until December 2016. Demographic characteristics, responses, progression-free survival (PFS), overall survival (OS), and ADRs were recorded.
RESULT
A total of 48 patients with stage IV lung adenocarcinoma harboring susceptible EGFR mutations who received afatinib as their first-line therapy were enrolled. Patients using 30 mg daily as the initial dose tended to be older and female and have a smaller body size. The patients using 30 mg of afatinib daily as their initial dose had a similar response rate to those receiving 40 mg daily (76% vs. 95%, p = 0.0862) and the same disease control rate (100% vs. 100%, p = 0.1486). The PFS was similar between the patients receiving 30 mg or 40 mg of afatinib daily (median PFS: 469 vs. 443 days, log-rank p = 0.8418). Patients receiving 30 mg daily had a significantly lower incidence of diarrhea than those using 40 mg daily (41% vs. 100%, p < 0.0001).
CONCLUSION
An initial afatinib dose of 30 mg daily had similar response and progression-free survival rates as an initial dose of 40 mg daily, but resulted in fewer serious ADRs in this study.
背景
阿法替尼是第二代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）。与细胞毒性化疗相比，阿法替尼已被证明在治疗携带EGFR突变的非小细胞肺癌方面具有更好的疗效。然而，每日40毫克的初始剂量常伴有严重的药物不良反应（ADR），28%至53.3%的患者需要减量。此前尚无研究比较阿法替尼不同初始剂量（每日40毫克与30毫克）在肺癌治疗中的临床疗效和ADR。
方法
确定2014年5月至2016年8月期间在台湾高雄医学大学附属的两家医院诊断并接受治疗的IV期肺腺癌患者，并随访至2016年12月。记录人口统计学特征、反应、无进展生存期（PFS）、总生存期（OS）和ADR。
结果
共有48例携带敏感EGFR突变的IV期肺腺癌患者接受阿法替尼作为一线治疗。初始剂量为每日30毫克的患者往往年龄较大、为女性且体型较小。初始剂量为每日30毫克阿法替尼的患者与每日接受40毫克的患者具有相似的缓解率（76%对95%，p = 0.0862）和相同的疾病控制率（100%对100%，p = 0.1486）。每日接受30毫克或40毫克阿法替尼的患者的PFS相似（中位PFS：469天对443天，对数秩检验p = 0.8418）。每日接受30毫克的患者腹泻发生率明显低于每日使用40毫克的患者（41%对100%，p < 0.0001）。
结论
在本研究中，阿法替尼每日初始剂量30毫克与每日初始剂量40毫克具有相似的缓解率和无进展生存率，但严重ADR较少。
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