Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Health Data Science, Tokyo Medical University, Tokyo, Japan.
Jpn J Clin Oncol. 2024 Jun 1;54(6):730-734. doi: 10.1093/jjco/hyae032.
Osimertinib is the standard of care for patients with epidermal growth factor receptor-activating mutation-positive non-small cell lung cancer. Dose-toxicity has been previously reported, but no dose-response data within the range of 20-240 mg daily (mg/d). Thus, the current 80 mg/d dosing might be too high for elderly Japanese patients with an average body weight of only 50 kg, resulting in excessive toxicity and cost. We therefore initiated a study to investigate whether osimertinib at 40 mg/d is non-inferior to 80 mg/d in patients with advanced or recurrent epidermal growth factor receptor-activating mutation-positive non-small cell lung cancer aged ≥70 years, using a regression discontinuity design. Osimertinib is administered at 40 mg/d for body weight ≤50 kg, and 80 mg/d for body weight >50 kg. The primary endpoint is progression-free survival. Sample size is 550 patients, based on a non-inferiority margin of the progression-free survival hazard ratio 1.333, 0.10 one-sided type I error and 80% power.
奥希替尼是表皮生长因子受体激活突变阳性非小细胞肺癌患者的标准治疗方法。先前已经报道了剂量毒性，但在每日 20-240mg 的范围内没有剂量反应数据。因此，目前每天 80mg 的剂量对于平均体重仅为 50kg 的老年日本患者来说可能过高，导致毒性和成本过高。因此，我们开始了一项研究，旨在使用回归间断设计调查奥希替尼每天 40mg 是否不劣于 80mg 用于治疗年龄≥70 岁的晚期或复发性表皮生长因子受体激活突变阳性非小细胞肺癌患者。对于体重≤50kg 的患者，奥希替尼的剂量为 40mg/d，对于体重>50kg 的患者，奥希替尼的剂量为 80mg/d。主要终点是无进展生存期。基于无进展生存风险比 1.333、0.10 单侧类型 I 错误和 80%功效的非劣效性边界，样本量为 550 例患者。
