剂量调整对参与LUX-Lung临床试验项目的中国突变型非小细胞肺癌患者使用阿法替尼的安全性和疗效的影响。
Effect of Dose Adjustments on the Safety and Efficacy of Afatinib in Chinese Patients with Mutated Non-Small Cell Lung Cancer Who Participated in the LUX-Lung Clinical Trial Program.
作者信息
Tu Hai-Yan, Wu Yi-Long
机构信息
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China.
出版信息
Onco Targets Ther. 2020 Dec 7;13:12539-12547. doi: 10.2147/OTT.S273866. eCollection 2020.
BACKGROUND
Post hoc analysis of the LUX-Lung 3 and 6 (LL3/6) Phase III trials showed that tolerability-guided dose-adjustments of afatinib reduced treatment-related adverse events (TRAEs) without affecting progression-free survival (PFS) in patients with epidermal growth factor receptor () mutation-positive non-small-cell lung cancer (NSCLC). The current post hoc analysis evaluated outcomes of tolerability-guided dose adjustments of afatinib in patients enrolled in the LL3/6/7 trials in Chinese centers.
PATIENTS AND METHODS
Patients enrolled in LL3/6/7 had advanced mutation-positive NSCLC. LL3 and LL7 recruited patients globally (including China) and LL6 enrolled Asian patients from China, Thailand, and South Korea. In LL3 and LL6, patients were randomized to afatinib 40 mg/day or cisplatin-based chemotherapy. In the Phase IIb LL7 trial, patients were randomized to afatinib 40 mg/day or gefitinib. Tolerability-guided dose adjustments were permitted for TRAEs, and PFS was the primary endpoint. This post hoc analysis pooled data from patients enrolled in Chinese centers in LL3/6/7 and analyzed the frequency and severity of TRAEs before and after afatinib dose reductions during the first 6 months. PFS and overall survival (OS) were compared for patients who had a dose reduction in the first 6 months and those who did not.
RESULTS
Overall, 299 patients were enrolled in Chinese centers; 68 (23%) had afatinib dose reductions to <40 mg/day in the first 6 months. Prior to dose reduction, 55/68 patients (81%) experienced grade ≥3 TRAE versus 13/68 (19%) after dose reduction. Grade ≥3 TRAEs were much more common in patients with than in those without dose reduction. Median PFS was 11.0 months in both groups, and median OS did not differ significantly: 23.1 months in patients with a dose reduction and 26.9 months in those without a dose reduction.
CONCLUSION
Tolerability-guided afatinib dose adjustment is an effective strategy to reduce TRAEs without affecting efficacy in Chinese patients.
背景
LUX-Lung 3和6（LL3/6）III期试验的事后分析表明，对于表皮生长因子受体（EGFR）突变阳性的非小细胞肺癌（NSCLC）患者，阿法替尼基于耐受性的剂量调整可减少治疗相关不良事件（TRAEs），且不影响无进展生存期（PFS）。本次事后分析评估了在中国中心入组LL3/6/7试验的患者中，阿法替尼基于耐受性的剂量调整的结果。
患者与方法
入组LL3/6/7的患者患有晚期EGFR突变阳性NSCLC。LL3和LL7在全球范围（包括中国）招募患者，LL6在中国、泰国和韩国招募亚洲患者。在LL3和LL6中，患者被随机分为阿法替尼40mg/天或基于顺铂的化疗组。在IIb期LL7试验中，患者被随机分为阿法替尼40mg/天或吉非替尼组。允许对TRAEs进行基于耐受性的剂量调整，PFS为主要终点。本次事后分析汇总了在LL3/6/7中国中心入组患者的数据，并分析了前6个月阿法替尼剂量降低前后TRAEs的发生频率和严重程度。比较了前6个月内进行剂量降低的患者和未进行剂量降低的患者的PFS和总生存期（OS）。
结果
总体而言，299例患者在中国中心入组；68例（23%）在头6个月内将阿法替尼剂量降至<40mg/天。剂量降低前，68例患者中有55例（81%）发生≥3级TRAE，剂量降低后为13例（19%）。≥3级TRAE在进行剂量降低的患者中比未进行剂量降低的患者更为常见。两组的中位PFS均为11.0个月，中位OS无显著差异：剂量降低的患者为23.1个月，未进行剂量降低的患者为26.9个月。
结论
对于中国患者，基于耐受性的阿法替尼剂量调整是减少TRAEs且不影响疗效的有效策略。
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