Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Br J Cancer. 2018 Jan;118(1):38-42. doi: 10.1038/bjc.2017.395. Epub 2017 Nov 16.

Abstract

Background: We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease.

Methods: Patients with crizotinib-pretreated locally advanced or metastatic disease received alectinib 600 mg orally twice daily in two phase II trials. All patients underwent baseline imaging and regular centrally reviewed scans.

Results: At 24 months, the CIR for CNS progression was lower in patients without vs with baseline CNS metastases (8.0 vs 43.9%). Patients with baseline CNS disease and prior radiotherapy had a higher CIR of CNS progression than radiotherapy-naive patients (50.5 vs 27.4%) and a lower CIR of non-CNS progression (25.8 vs 42.5%). Adverse events leading to withdrawal occurred in 5.9% and 6.7% of patients with and without baseline CNS metastases, respectively.

Conclusions: This analysis indicates a potential role for alectinib in controlling and preventing CNS metastases.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase / genetics*
  • Carbazoles / administration & dosage*
  • Carbazoles / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / epidemiology
  • Central Nervous System Neoplasms / secondary
  • Disease Progression
  • Female
  • Humans
  • Incidence
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Piperidines / administration & dosage*
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Carbazoles
  • Piperidines
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • alectinib