一项 afatinib 低起始剂量作为 EGFR 突变阳性非小细胞肺癌（KTORG1402）一线治疗的 II 期研究。

A phase II study of low starting dose of afatinib as first-line treatment in patients with EGFR mutation-positive non-small-cell lung cancer (KTORG1402).

机构信息

Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.

Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan; Department of Thoracic Oncology, Kansai Medical University Hospital, Hirakata, Japan.

出版信息

Lung Cancer. 2019 Sep;135:175-180. doi: 10.1016/j.lungcan.2019.03.030. Epub 2019 Mar 28.

DOI:10.1016/j.lungcan.2019.03.030

PMID:31446992

Abstract

OBJECTIVES

Afatinib is an effective treatment in patients who have epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), but its toxicities often require dose adjustment. Exploratory analyses of previous trials have suggested that reducing the dose of afatinib can decrease treatment-related adverse events without negatively affecting effectiveness. The aim of this study was to assess the efficacy and safety of low starting dose of afatinib with dose modification according to its toxicity in patients with EGFR mutation-positive NSCLC.

MATERIALS AND METHODS

This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib starting in a dose of 20 mg/day. If tolerated, the dose was increased in 10-mg increments up to 50 mg/day. The primary endpoint was progression-free survival (PFS).

RESULTS

From February 2015 through March 2016, 46 patients were enrolled. The median age was 73 years (range, 43-86), and 35 patients (72%) were women.EGFR mutation subtypes included exon 19 deletion (54%) and Leu858Arg point mutation (46%). Most patients had a performance status of 0 or 1 (91%) and a histological diagnosis of adenocarcinoma (98%). As of the data cut-off date of June 2017, the median follow-up was 18.9 months. The median PFS was 15.2 months (95% CI: 13.2-not estimable). The 1-year overall survival rate was 95.6% (95% CI: 89.7%-100%). The objective response rate was 81.8% (95% CI, 81.3%-98.6%). Adverse events of grade 3 or higher occurred in 14 patients (30.4%) and included rash/acne in 4 patients (8.7%), paronychia in 4 patients (8.7%), diarrhea in 2 patients (4.3%). There was no treatment-related death.

CONCLUSIONS

Low starting dose of afatinib therapy showed promising clinical efficacy and good tolerability. Further investigations are warranted.

摘要

目的

阿法替尼是治疗表皮生长因子受体（EGFR）突变阳性非小细胞肺癌（NSCLC）患者的有效药物，但它的毒性通常需要调整剂量。先前试验的探索性分析表明，降低阿法替尼的剂量可以减少治疗相关的不良反应，而不会对疗效产生负面影响。本研究旨在评估在 EGFR 突变阳性 NSCLC 患者中使用低起始剂量的阿法替尼并根据其毒性进行剂量调整的疗效和安全性。

材料和方法

这是一项多中心、单臂、开放标签的 II 期临床试验。初治的晚期 NSCLC 患者存在常见的 EGFR 突变，接受阿法替尼起始剂量为 20mg/天。如果耐受，剂量可增加 10mg，最高增至 50mg/天。主要终点是无进展生存期（PFS）。

结果

从 2015 年 2 月至 2016 年 3 月，共纳入 46 例患者。中位年龄为 73 岁（范围：43-86 岁），35 例（72%）为女性。EGFR 突变亚型包括外显子 19 缺失（54%）和 Leu858Arg 点突变（46%）。大多数患者的体能状态为 0 或 1（91%），组织学诊断为腺癌（98%）。截至 2017 年 6 月数据截止日期，中位随访时间为 18.9 个月。中位 PFS 为 15.2 个月（95%CI：13.2-不可估计）。1 年总生存率为 95.6%（95%CI：89.7%-100%）。客观缓解率为 81.8%（95%CI，81.3%-98.6%）。3 级或以上不良反应发生在 14 例患者（30.4%）中，包括皮疹/痤疮 4 例（8.7%）、甲沟炎 4 例（8.7%）、腹泻 2 例（4.3%）。无治疗相关死亡。