Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK -positive non-small-cell lung cancer

ESMO Open

article

J. Wolf¹  Å. Helland²  I.-J. Oh³  M.R. Migliorino⁴  R. Dziadziuszko⁵  A. Wrona⁵  J. de Castro⁶  J. Mazieres⁷  F. Griesinger⁸  M. Chlistalla⁹  A. Cardona⁹  T. Ruf⁹  K. Trunzer⁹  V. Smoljanovic⁹  S. Novello^1,10 

[1] Department I of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne;Department of Cancer Genetics and Department of Oncology, Institute for Cancer Research, Oslo University Hospital, University of Oslo;Department of Internal Medicine, Chonnam National University Medical School;Pulmonary Oncology Unit, Azienda Ospedaliera San Camillo Forlanini Hospital;Department of Oncology and Radiotherapy, Medical University of Gdansk;Department of Medical Oncology, La Paz University Hospital;Department of Pneumology, Toulouse University Hospital, Paul Sabatier University;Department of Hematology and Oncology, Pius Hospital, University Medicine Oldenburg;F. Hoffmann-La Roche Ltd.;Department of Oncology, University of Turin

关键词: ALK-positive NSCLC;    ALUR;    alectinib;    chemotherapy;    TP53;   

DOI  :  10.1016/j.esmoop.2021.100333

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling.Patients and methods Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes.Results Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93).Conclusions Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.

【 授权许可】

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