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2026年8月25日星期二
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辅助阿来替尼对比化疗用于切除的ALK阳性非小细胞肺癌(ALINA):随机、开放标签、III期试验的健康相关生活质量与安全性结果

Adjuvant alectinib versus chemotherapy in resected ALK-positive non-small-cell lung cancer (ALINA): health-related quality-of-life and safety outcomes from a randomised, open-label, phase 3 trial.

期刊
The Lancet
PMID
42636834
原文
PubMed ↗
发布日期

作者

  • Rafal Dziadziuszko — Department of Oncology & Radiotherapy and Early Phase Clinical Trials Centre, Medical University of Gdansk, Gdańsk, Poland. Electronic address: rafald@gumed.edu.pl.
  • Jin Seok Ahn — Department of Hematology & Oncology, Samsung Medical Center, Seoul, South Korea.
  • Fabrice Barlesi — Department of Medical Oncology, International Center for Thoracic Cancers, Gustave Roussy, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France.
  • Benjamin J Solomon — Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
  • Yi-Long Wu — Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Igor Bondarenko — Oncology and Medical Radiology, Dnipro State Medical University, Dnipro, Ukraine.
  • Maximilian Hochmair — Department of Respiratory & Critical Care Medicine, Karl-Landsteiner-Institute of Lung Research & Pulmonary Oncology, Clinic Floridsdorf, Vienna, Austria.
  • Hidehito Horinouchi — Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
  • Dae Ho Lee — Asan Medical Center, Seoul, South Korea.
  • Jong-Seok Lee — Seoul National University Bundang Hospital, Seongnam, South Korea.
  • David Planchard — Department of Medical Oncology, International Center for Thoracic Cancers, Gustave Roussy, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France.
  • Achim Rittmeyer — Lungenfachklinik Immenhausen, Immenhausen, Germany.
  • Wenzhao Zhong — Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Leah Adler — Global PD Medical Affairs (Oncology), F Hoffmann-La Roche, Basel, Switzerland.
  • Venice Archer — PD Oncology, Roche Products, Welwyn Garden City, UK.
  • Andres Cardona — Data and Statistical Sciences, F Hoffmann-La Roche, Basel, Switzerland.
  • Patricia Petric — Product Development Safety, F Hoffmann-La Roche, Basel, Switzerland.
  • Astrid Scalori — PD Oncology, Roche Products, Welwyn Garden City, UK.
  • Beiying Ding — Biostatistics, Genentech, South San Francisco, CA, USA.
  • Carla Mamolo — Patient-Centered Outcomes Research, Genentech, South San Francisco, CA, USA.
  • Vlatka Smoljanovic — Global PD Medical Affairs (Oncology), F Hoffmann-La Roche, Basel, Switzerland.
  • Makoto Nishio — Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

作者单位

  • Department of Oncology & Radiotherapy and Early Phase Clinical Trials Centre, Medical University of Gdansk, Gdańsk, Poland. Electronic address: rafald@gumed.edu.pl.
  • Department of Hematology & Oncology, Samsung Medical Center, Seoul, South Korea.
  • Department of Medical Oncology, International Center for Thoracic Cancers, Gustave Roussy, Villejuif, France; Paris Saclay University, Faculty of Medicine, Kremlin-Bicêtre, France.
  • Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
  • Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Oncology and Medical Radiology, Dnipro State Medical University, Dnipro, Ukraine.
  • Department of Respiratory & Critical Care Medicine, Karl-Landsteiner-Institute of Lung Research & Pulmonary Oncology, Clinic Floridsdorf, Vienna, Austria.
  • Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
  • Asan Medical Center, Seoul, South Korea.
  • Seoul National University Bundang Hospital, Seongnam, South Korea.
  • Lungenfachklinik Immenhausen, Immenhausen, Germany.
  • Global PD Medical Affairs (Oncology), F Hoffmann-La Roche, Basel, Switzerland.
  • PD Oncology, Roche Products, Welwyn Garden City, UK.
  • Data and Statistical Sciences, F Hoffmann-La Roche, Basel, Switzerland.
  • Product Development Safety, F Hoffmann-La Roche, Basel, Switzerland.
  • Biostatistics, Genentech, South San Francisco, CA, USA.
  • Patient-Centered Outcomes Research, Genentech, South San Francisco, CA, USA.
  • Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

摘要

中文

对于已切除的ALK阳性非小细胞肺癌(NSCLC)患者,在全球 III 期、开放标签、随机 ALINA 试验中,辅助阿来替尼与铂类化疗相比显著改善了无病生存期。我们报告了 ALINA 试验的安全性和健康相关生活质量(HRQoL)结局。符合条件的患者年龄≥18岁,患有已切除的、ALK阳性、IB(≥4cm)-IIIA期 NSCLC(根据美国癌症联合委员会和国际癌症控制联盟癌症分期手册第7版)且美国东部肿瘤协作组体能状态评分为0-1,通过分层随机化方法按1:1比例随机分配接受口服阿来替尼(600 mg 每日两次)治疗24个月或静脉铂类化疗4个周期(每周期3周)。随机化按疾病分期和种族分层。主要终点(先前已报告)为无病生存期。安全性是次要终点,HRQoL是探索性终点。安全性由研究者根据国家癌症研究所不良事件通用术语标准5.0版评估,直至最后一次阿来替尼给药或化疗周期后28天。HRQoL通过简短36项健康调查问卷第2版(SF-36v2)在基线、每3周至第12周、随后每12周直至疾病复发、同意退出、死亡或第96周时评估。采用基于常模的评分;临床有意义的改变根据SF-36v2手册定义。安全性和HRQoL分别在安全性可评估人群和意向治疗人群中评估。本研究已在ClinicalTrials.gov注册(NCT03456076),正在进行中。2018年8月16日至2021年12月8日期间,257例患者被分配接受阿来替尼(n=130)或化疗(n=127)。123例(48%)为男性,134例(52%)为女性;143例(56%)为亚洲人。安全性可评估人群包括128例接受阿来替尼的患者和120例接受化疗的患者;阿来替尼组中位安全性随访时间为24.8个月(IQR 22.0-24.9),化疗组为3.7个月(IQR 3.7-3.8)。辅助阿来替尼的安全性总体与其已知特征一致。阿来替尼组最常见的3-4级不良事件为血肌酸磷酸激酶升高(8/128,6%)、丙氨酸氨基转移酶升高(2/128,2%)和血胆红素升高(2/128,2%);化疗组为中性粒细胞计数降低(12/120,10%)、中性粒细胞减少(10/120,8%)和恶心(5/120,4%)。阿来替尼组有2例(2%)患者发生严重治疗相关不良事件(分别为阑尾炎和肺炎),化疗组有8例(7%)患者发生(最常见为胃肠道疾病,3例[3%])。两组均无不良事件导致的死亡。阿来替尼组因不良事件停药的患者较化疗组少(7例[5%]对15例[13%])。在第12周,阿来替尼在躯体疼痛、角色生理、心理健康、社会功能和活力SF-36v2领域较基线出现有临床意义的改善;在2年积极治疗期间,身体和精神HRQoL改善得以维持(第96周时,心理成分总结平均分为49.9[SD 10.4];生理成分总结平均分为48.8[SD 7.2]),并达到与一般人群相似的水平(人群常模:50)。对于已切除的ALK阳性NSCLC患者,辅助阿来替尼的安全性可控;HRQoL在2年积极治疗期间改善并得以维持。结合ALINA试验中观察到的无病生存获益,这些数据支持辅助阿来替尼成为已切除的ALK阳性NSCLC患者的重要新标准治疗。F Hoffmann-La Roche。

English

For patients with resected, ALK-positive non-small-cell lung cancer (NSCLC), adjuvant alectinib significantly improved disease-free survival versus platinum-based chemotherapy in the global, phase 3, open-label, randomised ALINA trial. We report safety and health-related quality-of-life (HRQoL) outcomes from the ALINA trial. Eligible patients aged 18 years or older with resected, ALK-positive, stage IB (≥4 cm)-IIIA NSCLC (per the American Joint Committee on Cancer and the Union for International Cancer Control Cancer Staging Manual 7th edition) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (1:1) via a block-stratified randomisation method to receive oral alectinib (600 mg twice daily) for 24 months or intravenous platinum-based chemotherapy for four 3-week cycles. Randomisation was stratified according to disease stage and race. The primary endpoint, previously reported, was disease-free survival. Safety was a secondary endpoint and HRQoL was an exploratory endpoint. Safety was assessed by the investigator as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5·0 until 28 days after the last alectinib dose or chemotherapy cycle. HRQoL was assessed via the Short-Form 36-item health survey version 2 (SF-36v2) questionnaire at baseline, every 3 weeks to week 12, then every 12 weeks until disease recurrence, consent withdrawal, death, or week 96. Norm-based scoring was applied; clinically meaningful changes were defined using the SF-36v2 manual. Safety was assessed in the safety-evaluable population and HRQoL in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT03456076) and is ongoing. Between Aug 16, 2018, and Dec 8, 2021, 257 patients were assigned to receive alectinib (n=130) or chemotherapy (n=127). 123 (48%) patients were male and 134 (52%) were female; 143 (56%) were Asian. The safety-evaluable population comprised 128 patients who received alectinib and 120 patients who received chemotherapy; median duration of safety follow-up was 24·8 months (IQR 22·0-24·9) in the alectinib group and 3·7 months (IQR 3·7-3·8) in the chemotherapy group. The safety of adjuvant alectinib was generally consistent with its known profile. The most common grade 3-4 adverse events were blood creatine phosphokinase increased (eight [6%] of 128), alanine aminotransferase increased (two [2%] of 128), and blood bilirubin increased (two [2%] of 128) in the alectinib group, and neutrophil count decreased (12 [10%] of 120), neutropenia (ten [8%] of 120), and nausea (five [4%] of 120) in the chemotherapy group. Serious treatment-related adverse events occurred in two (2%; one each with appendicitis and pneumonitis) of 128 patients in the alectinib group and eight (7%) of 120 patients in the chemotherapy group ( most common were gastrointestinal disorders in three [3%] patients). No deaths due to adverse events were reported in either group. There were fewer discontinuations due to adverse events with alectinib (seven [5%]) versus chemotherapy (15 [13%]). A clinically meaningful difference in improvement from baseline was seen at week 12 for bodily pain, role physical, mental health, social functioning, and vitality SF-36v2 domains with alectinib; improvements in physical and mental HRQoL were maintained over 2 years of active treatment (at week 96, mean Mental Component Summary score: 49·9 [SD 10·4]; mean Physical Component Summary score: 48·8 [SD 7·2]) and reached levels similar to the general population (population norm: 50). For patients with resected ALK-positive NSCLC, adjuvant alectinib had a manageable safety profile; HRQoL improved and was maintained over 2 years of active treatment. Together with the disease-free survival benefit seen in ALINA, these data support adjuvant alectinib as an important new standard-of-care for patients with resected ALK-positive NSCLC. F Hoffmann-La Roche.

分类与指标

研究类型
临床研究
病种
肺癌
JCR 分区
Q1
影响因子
109.0
新锐分区
1区