Progression-Free and Overall Survival of Patients With ALK Rearrangement-Positive Non-Small Cell Lung Cancer Treated Sequentially With Crizotinib and Alectinib

Clin Lung Cancer. 2016 Nov;17(6):528-534. doi: 10.1016/j.cllc.2016.05.001. Epub 2016 May 18.


Introduction: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show marked therapeutic efficacy in patients with non-small cell lung cancer (NSCLC) harboring the echinoderm microtubule-associated protein-like 4-ALK fusion gene. The effect on overall survival (OS) of sequential treatment with the first- and second-generation ALK-TKIs crizotinib and alectinib, respectively, has remained unknown. We have examined the clinical outcome of such sequential treatment in a retrospective analysis of patients with ALK-rearranged NSCLC.

Materials and methods: Eleven patients with ALK-rearranged NSCLC treated with crizotinib followed by alectinib were identified. The progression-free survival (PFS) and OS for these patients were determined from a retrospective review of their medical records.

Results: The median PFS on crizotinib or alectinib was 6.1 months (range, 1.0-15.4 months) and 15.2 months (range, 1.0-28.3 months), respectively. The median combined PFS for both crizotinib and alectinib was 18.2 months (range, 10.4-43.7 months). Crizotinib was continued beyond radiographic evidence of progressive disease in 6 of the 11 patients, with a median duration of postprogression crizotinib treatment of 9.4 months (range, 0-20.5 months). The OS period from the diagnosis of metastatic disease or the initiation of crizotinib treatment was 51.1 months (range, 20.9-69.5 months) and 48.6 months (range, 19.8-50.1 months), respectively.

Conclusion: Our retrospective study has revealed durable survival for alectinib treatment after crizotinib failure in patients with ALK-rearranged NSCLC.

Keywords: ALK-TKI; Anaplastic lymphoma kinase; NSCLC; OS; PFS.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase
  • Biomarkers, Tumor / genetics
  • Carbazoles / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Crizotinib
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Piperidines / therapeutic use
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Retrospective Studies
  • Survival Rate
  • Young Adult


  • Biomarkers, Tumor
  • Carbazoles
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • alectinib