Transformation to SCLC after Treatment with the ALK Inhibitor Alectinib

J Thorac Oncol. 2016 Jun;11(6):e67-72. doi: 10.1016/j.jtho.2015.12.105. Epub 2016 Jan 2.


We report an anaplastic lymphoma receptor tyrosine kinase gene (ALK)-positive patient who showed a paradoxical response to the ALK inhibitor alectinib; the primary lesion increased in size, whereas other metastatic lesions decreased markedly. A biopsy of the primary lesion confirmed an ALK rearrangement; however, the tumor had transformed histologically into small cell lung cancer. The lack of reports of small cell lung cancer transformation in ALK-positive patients implies that this outcome was unusual; this patient was treated with alectinib, which is more selective and has a greater inhibitory effect than crizotinib. This case may reveal resistance mechanisms that differ according to the agent used for treatment.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Anaplastic Lymphoma Kinase
  • Carbazoles / adverse effects*
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / pathology*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Piperidines / adverse effects*
  • Protein Kinase Inhibitors / adverse effects
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Small Cell Lung Carcinoma / chemically induced
  • Small Cell Lung Carcinoma / pathology*


  • Carbazoles
  • Piperidines
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • alectinib