表皮生长因子受体（EGFR）突变类型是否影响晚期 EGFR 突变阳性非小细胞肺癌患者的患者报告结局？阿法替尼与化疗（LUX-Lung 3 和 LUX-Lung 6）比较的两项大型 III 期研究的分析。

Does EGFR Mutation Type Influence Patient-Reported Outcomes in Patients with Advanced EGFR Mutation-Positive Non-Small-Cell Lung Cancer? Analysis of Two Large, Phase III Studies Comparing Afatinib with Chemotherapy (LUX-Lung 3 and LUX-Lung 6).

机构信息

Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

McGill University, Montreal, Canada.

出版信息

Patient. 2018 Feb;11(1):131-141. doi: 10.1007/s40271-017-0287-z.

INTRODUCTION

In LUX-Lung 3 and LUX-Lung 6, afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with tumors harboring common epidermal growth factor receptor (EGFR) mutations (Del19/L858R) and significantly improved overall survival (OS) in patients with tumors harboring Del19 mutations. Patient-reported outcomes stratified by EGFR mutation type are reported.

PATIENTS AND METHODS

Lung cancer symptoms and health-related quality of life (QoL) were assessed every 21 days until progression using the EORTC Quality of Life Core Questionnaire C30 and its lung cancer-specific module, LC13. Analyses of cough, dyspnea, and pain were prespecified and included analysis of percentage of patients who improved on therapy, time to deterioration of symptoms, and change over time. Global health status (GHS)/QoL was also assessed. Analyses were conducted for all patients with tumors harboring Del19 or L858R mutations and were exploratory.

RESULTS

Compared with chemotherapy, afatinib more commonly improved symptoms of, delayed time to deterioration for, and was associated with better mean scores over time for cough and dyspnea in patients with Del19 or L858R mutations. All three prespecified analyses of pain showed a trend favoring afatinib over chemotherapy. In both Del19 and L858R mutations, afatinib was also associated with improvements in GHS/QoL. Longitudinal analyses demonstrated statistically significant improvements in GHS/QoL for afatinib over chemotherapy for patients with tumors harboring Del19 mutations or L858R mutations.

CONCLUSIONS

These exploratory analyses suggest first-line afatinib improved lung cancer-related symptoms and GHS/QoL compared with chemotherapy in patients with non-small-cell lung cancer with tumors harboring common EGFR mutations, with benefits in both Del19 and L858R patients. When considered with OS (Del19 patients only) and PFS benefits, these findings substantiate the value of using afatinib over chemotherapy in these patient groups.

介绍

在 LUX-Lung 3 和 LUX-Lung 6 研究中，阿法替尼较化疗显著改善了具有常见表皮生长因子受体（EGFR）突变（Del19/L858R）的肿瘤患者的无进展生存期（PFS），并显著改善了具有 Del19 突变的肿瘤患者的总生存期（OS）。报告了按 EGFR 突变类型分层的患者报告的结局。

方法

使用 EORTC 生活质量核心问卷 C30 及其肺癌专用模块 LC13，每 21 天评估一次肺癌症状和健康相关生活质量（QoL），直至进展。对咳嗽、呼吸困难和疼痛进行了预设分析，包括分析治疗后改善的患者比例、症状恶化的时间以及随时间的变化。还评估了总体健康状况（GHS）/QoL。对携带 Del19 或 L858R 突变的所有患者进行了分析，且为探索性分析。

结果

与化疗相比，阿法替尼更常见地改善了携带 Del19 或 L858R 突变的患者的咳嗽和呼吸困难症状，延迟了症状恶化的时间，并且随时间的推移，平均评分更好。所有三种预设的疼痛分析均显示阿法替尼优于化疗的趋势。在 Del19 和 L858R 突变中，阿法替尼也与 GHS/QoL 的改善相关。对于携带 Del19 突变或 L858R 突变的肿瘤患者，与化疗相比，阿法替尼的纵向分析显示 GHS/QoL 有统计学意义的改善。