Vol 17, No 6 (2021)
Review paper
Published online: 2021-10-01

open access

Page views 5902
Article views/downloads 358
Get Citation

Connect on Social Media

Connect on Social Media

The role of diagnostics and treatment — lung cancer with ALK rearrangement

Katarzyna Stencel12, Renata Langfort3, Rodryg Ramlau12
Oncol Clin Pract 2021;17(6):253-262.


Lung cancer is the most common cause of cancer-related deaths both in Poland and worldwide. Recently, the incidence of lung adenocarcinoma has been increasing and currently it accounts for about 45% of all diagnosed lung cancers. Patients diagnosed with non-squamous non-small cell lung cancer (NSCLC), especially with adenocarcinoma, cancer containing adenocarcinoma component, large cell carcinoma, as well as patients with not otherwise specified (NOS) cancer may benefit from targeted therapy if molecular tests confirm the presence of activating EGFR gene mutations, ALK, ROS1 or NTRK rearrangement, or BRAF gene mutations. The ALK gene rearrangement is a positive predictive marker of tyrosine kinase inhibitors (TKIs) effectiveness, which are more effective than standard chemotherapy in this population, are associated with improving the quality of life and also indicate a different, more tolerable toxicity profile. This study presents the diagnostic sequence and registered treatment options for patients with ALK-positive NSCLC.

Article available in PDF format

View PDF Download PDF file


  1. Lindeman N, Cagle P, Aisner D, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med. 2018; 142(3): 321–346.
  2. Travis WD, Brambilla E, Burke AP, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 2015; International Agency for Research on Cancer. Lyon.
  3. Kim H, Chung JH. Overview of clinicopathological features of ALK-rearranged lung adenocarcinoma and current diagnostic testing for ALK-rearrangement.
  4. Planchard D, Popat S, Kerr K, et al. ESMO Guidelines Committee, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29 Suppl 4(Suppl 4): iv192–iv237.
  5. Kalemkerian GP, et al. Narula N Kennedy EB : Molecular testing guideline for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018; 36: 911–919.
  6. Travis WD, Nicholson AG, Geisinger KR, et al. Tumors of the Lower Respiratory Tract. AFIP Atlas of Tumor Pathology. Series 4. 2019. American Registry of Pathology, Arlington, Virginia.
  7. Yatabe Y, Dacic S, Borczuk AC, et al. Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Oncol. 2019; 14(3): 377–407.
  8. Mok TS, Carbone D, Hirsch FR. IASLC Atlas of EGFR Testing in Lung Cancer. Aurora, CO: International Association for the Study of Lung Cancer. 2017.
  9. Tsao MS, Hirsch FR, Yatabe Y. IASLC Atlas of ALK and ROS1 Testing in Lung Cancer. Second Edition. Aurora, CO: International Association for the Study of Lung Cancer. 2017.
  10. Shaw AT, Engelman JA. ALK in lung cancer: past, present, and future. J Clin Oncol. 2013; 31(8): 1105–1111.
  11. Ou SH, Zhu V, Nagasaka M. Catalog of 5’ fusion partners in ALK-positive NSCLC circa 2020. JTO Clinical and Research Reports. 2020; 1(1): 100015.
  12. Sholl LM, Weremowicz S, Gray SW, et al. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol. 2013; 8(3): 322–328.
  13. Tsao MS, Yatabe Y. Old soldiers never die: is there still a role for immunohistochemistry in the era of next-generation sequencing panel testing? J Thorac Oncol. 2019; 14(12): 2035–2038.
  14. Solomon BJ, Mok T, Kim DW, et al. PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014; 371(23): 2167–2177.
  15. Solomon BJ, Kim DW, Wu YL, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018; 36(22): 2251–2258.
  16. Peters S, Camidge DR, Shaw AT, et al. ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017; 377(9): 829–838.
  17. Camidge D, Peters S, Mok T, et al. Updated efficacy and safety data from the global phase III ALEX study of alectinib (ALC) versus crizotinib (CZ) in untreated advanced ALK+ NSCLC. ASCO 2018 Annual Meeting.
  18. Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017; 389(10072): 917–929.
  19. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018; 379(21): 2027–2039.
  20. Camidge R, Kim HR, Ahn MJ, et al. Brigatinib vs crizotinib in patients with ALK inhibitor-naive advanced ALK+ NSCLC: Updated results from the phase III ALTA-1L trial. ESMO Asia Congress, 2019.
  21. https://clinicaltrials.gov/ct2/show/NCT03052608.
  22. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013; 368(25): 2385–2394.
  23. Shaw AT, Gandhi L, Gadgeel S, et al. study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016; 17(2): 234–242.
  24. Novello S, Mazières J, Oh IJ, et al. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018; 29(6): 1409–1416.
  25. Kim DW, Tiseo M, Ahn MJ, et al. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol. 2017; 35(22): 2490–2498.
  26. Huber RM, Hansen KH, Paz-Ares Rodríguez L, et al. Brigatinib in crizotinib-refractory ALK+ NSCLC: 2-year follow-up on systemic and intracranial outcomes in the phase 2 ALTA trial. J Thorac Oncol. 2020; 15(3): 404–415.
  27. Shaw AT, Kim TM, Crinò L, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017; 18(7): 874–886.
  28. Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018; 19(12): 1654–1667.
  29. Wrona A, Dziadziuszko R, Jassem J. Management of brain metastases in non-small cell lung cancer in the era of tyrosine kinase inhibitors. Cancer Treat Rev. 2018; 71: 59–67.
  30. Duruisseaux M, Besse B, Cadranel J, et al. Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study. Oncotarget. 2017; 8(13): 21903–21917.
  31. Cho B, Kim DW, Bearz A, et al. ASCEND-8: a randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cel lung cancer. (NSCLC).
  32. Hou H, Sun D, Liu K, et al. The safety and serious adverse events of approved ALK inhibitors in malignancies: a meta-analysis. Cancer Manag Res. 2019; 11: 4109–4118.
  33. Zhu Q, Hu H, Weng DS, et al. Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC. BMC Cancer. 2017; 17(1): 412.
  34. Camidge DR, Dziadziuszko R, Peters S, et al. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated alk-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 2019; 14(7): 1233–1243.
  35. https://www.gov.pl/web/zdrowie/choroby-onkologiczne.