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. 2022 Feb;7(1):100333. doi: 10.1016/j.esmoop.2021.100333. Epub 2022 Jan 15.


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.

Keywords: ALK-positive NSCLC; ALUR; TP53; alectinib; chemotherapy.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Carbazoles
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Crizotinib / adverse effects
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Piperidines


  • Carbazoles
  • Piperidines
  • Crizotinib
  • Anaplastic Lymphoma Kinase
  • alectinib