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Diagnosis and Treatment of ALK Aberrations in Metastatic NSCLC

  • Lung Cancer (HA Wakelee, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

There has been rapid progress in the use of targeted therapies for ALK-positive which has led to improve dramatically PFS and OS in the metastatic ALK-rearranged NSCLC patients. There are several molecules now available (crizotinib, ceritinib, brigatinib, alectinib, and lorlatinib) and others in development. Such an improvement in treatment efficacy has even more highlighted the importance of an adequate identification of ALK alterations. Efficient and easily accessible testing tools are required to identify eligible patients in a timely fashion. Different methods for detecting ALK+ NSCLC patients are now available, with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) currently representing validated diagnostic techniques for the initial assessment of ALK status. Furthermore the widespread use of next-generation sequencing to detect other possible different activating mutations has allowed to identify individual ALK fusion variants. Several more expensive and time-consuming methods are also available nowadays which have the advantage to detect even rarer uncommon ALK fusion variants and mutations in tumour or blood samples. A review of the evolving testing-treatment landscape is needed to highlight the importance of properly diagnosing and treating this group of patients.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:•• Of major importance

  1. Banna GL, Passiglia F, Colonese F, et al. Immune-checkpoint inhibitors in non-small cell lung cancer: a tool to improve patients' selection. Crit Rev Oncol Hematol. 2018;129:27–39.

    Article  Google Scholar 

  2. Brahmer J HL, Jackman DM, et al. Five-year follow-up from the CA209–003 study of nivolumab in previously treated advanced non-small cell lung cancer: Clinical characteristics of long-term survivors. American Association for Cancer Research Annual Meeting, Washington, DC 2017 [abstract CT077].

  3. Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947–57.

    Article  CAS  Google Scholar 

  4. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239–46.

    Article  CAS  Google Scholar 

  5. Yang JC, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-lung 3 and LUX-lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16:141–51.

    Article  CAS  Google Scholar 

  6. Landi L, Tiseo M, Chiari R, et al. Activity of the EGFR-HER2 dual inhibitor afatinib in EGFR-mutant lung cancer patients with acquired resistance to reversible EGFR tyrosine kinase inhibitors. Clin Lung Cancer. 2014;15:411–7e414.

    Article  Google Scholar 

  7. Tsao AS, Scagliotti GV, Bunn PA Jr, et al. Scientific advances in lung Cancer 2015. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2016;11:613–38.

    Article  Google Scholar 

  8. Pikor LA, Ramnarine VR, Lam S, Lam WL. Genetic alterations defining NSCLC subtypes and their therapeutic implications. Lung Cancer. 2013;82:179–89.

    Article  Google Scholar 

  9. Addeo A, Tabbo F, Robinson T, et al. Precision medicine in ALK rearranged NSCLC: a rapidly evolving scenario. Crit Rev Oncol Hematol. 2018;122:150–6.

    Article  Google Scholar 

  10. Rodig SJ, Mino-Kenudson M, Dacic S, et al. Unique Clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the Western population. Clin Cancer Res. 2009;15:5216–23.

    Article  CAS  Google Scholar 

  11. Iwahara T, Fujimoto J, Wen D, et al. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene. 1997;14:439–49.

    Article  CAS  Google Scholar 

  12. Hallberg B, Palmer RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer. 2013;13:685–700.

    Article  CAS  Google Scholar 

  13. Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science. 1994;263:1281–4.

    Article  CAS  Google Scholar 

  14. Hallberg B, Palmer RH. The role of the ALK receptor in cancer biology. Ann Oncol. 2016;27:iii4–iii15.

    Article  Google Scholar 

  15. von Laffert M, Warth A, Penzel R, et al. Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9:1685–92.

    Article  Google Scholar 

  16. Guan J, Umapathy G, Yamazaki Y, et al. FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase. eLife. 2015;4:e09811.

    Article  Google Scholar 

  17. Wu YL, Planchard D, Lu S, et al. Pan-Asian adapted clinical practice guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS. Annals of Oncology : official journal of the European Society for Medical Oncology. 2019;30:171–210.

    Article  Google Scholar 

  18. von Laffert M, Warth A, Penzel R, et al. Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9:1685–92.

    Article  Google Scholar 

  19. Niu X, Chuang JC, Berry GJ, Wakelee HA. Anaplastic lymphoma kinase testing: IHC vs. FISH vs. NGS. Curr Treat Options in Oncol. 2017;18:71.

    Article  Google Scholar 

  20. Weickhardt AJ, Aisner DL, Franklin WA, et al. Diagnostic assays for identification of anaplastic lymphoma kinase-positive non-small cell lung cancer. Cancer. 2013;119:1467–77.

    Article  CAS  Google Scholar 

  21. Dacic S, Villaruz LC, Abberbock S, et al. ALK FISH patterns and the detection of ALK fusions by next generation sequencing in lung adenocarcinoma. Oncotarget. 2016;7:82943–52.

    Article  Google Scholar 

  22. Camidge DR, Kono SA, Flacco A, et al. Optimizing the detection of lung cancer patients harboring anaplastic lymphoma kinase (ALK) gene rearrangements potentially suitable for ALK inhibitor treatment. Clinical Cancer Research : an official journal of the American Association for Cancer Research. 2010;16:5581–90.

    Article  CAS  Google Scholar 

  23. Gao X, Sholl LM, Nishino M, et al. Clinical implications of variant ALK FISH rearrangement patterns. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2015;10:1648–52.

    Article  CAS  Google Scholar 

  24. Lambros MB, Natrajan R, Reis-Filho JS. Chromogenic and fluorescent in situ hybridization in breast cancer. Hum Pathol. 2007;38:1105–22.

    Article  CAS  Google Scholar 

  25. Tanner M, Gancberg D, Di Leo A, et al. Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am J Pathol. 2000;157:1467–72.

    Article  CAS  Google Scholar 

  26. Kim H, Yoo SB, Choe JY, et al. Detection of ALK gene rearrangement in non-small cell lung cancer: a comparison of fluorescence in situ hybridization and chromogenic in situ hybridization with correlation of ALK protein expression. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2011;6:1359–66.

    Article  Google Scholar 

  27. Hutarew G, Hauser-Kronberger C, Strasser F, et al. Immunohistochemistry as a screening tool for ALK rearrangement in NSCLC: evaluation of five different ALK antibody clones and ALK FISH. Histopathology. 2014;65:398–407.

    Article  Google Scholar 

  28. Marchetti A, Di Lorito A, Pace MV, et al. ALK protein analysis by IHC staining after recent regulatory changes: a comparison of two widely used approaches, revision of the literature, and a new testing algorithm. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2016;11:487–95.

    Article  Google Scholar 

  29. Cutz JC, Craddock KJ, Torlakovic E, et al. Canadian anaplastic lymphoma kinase study: a model for multicenter standardization and optimization of ALK testing in lung cancer. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9:1255–63.

    Article  CAS  Google Scholar 

  30. Lindeman NI, Cagle PT, Aisner DL, 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;142:321–46.

    Article  CAS  Google Scholar 

  31. Palmer RH, Vernersson E, Grabbe C, Hallberg B. Anaplastic lymphoma kinase: signalling in development and disease. Biochem J. 2009;420:345–61.

    Article  CAS  Google Scholar 

  32. Wiesner T, Lee W, Obenauf AC, et al. Alternative transcription initiation leads to expression of a novel ALK isoform in cancer. Nature. 2015;526:453–7.

    Article  CAS  Google Scholar 

  33. Wong DW, Leung EL, So KK, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer. 2009;115:1723–33.

    Article  CAS  Google Scholar 

  34. Pekar-Zlotin M, Hirsch FR, Soussan-Gutman L, et al. Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer. Oncologist. 2015;20:316–22.

    Article  Google Scholar 

  35. Soda M, Isobe K, Inoue A, et al. A prospective PCR-based screening for the EML4-ALK oncogene in non-small cell lung cancer. Clinical Cancer Research : an official journal of the American Association for Cancer Research. 2012;18:5682–9.

    Article  CAS  Google Scholar 

  36. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363:1693–703.

    Article  CAS  Google Scholar 

  37. Peled N, Palmer G, Hirsch FR, et al. Next-generation sequencing identifies and immunohistochemistry confirms a novel crizotinib-sensitive ALK rearrangement in a patient with metastatic non-small-cell lung cancer. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2012;7:e14–6.

    Article  CAS  Google Scholar 

  38. Choi YL, Takeuchi K, Soda M, et al. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res. 2008;68:4971–6.

    Article  CAS  Google Scholar 

  39. Beadling C, Wald AI, Warrick A, et al. A multiplexed amplicon approach for detecting gene fusions by next-generation sequencing. The Journal of Molecular Diagnostics : JMD. 2016;18:165–75.

    Article  CAS  Google Scholar 

  40. Früh M, Peters S. EML4-ALK variant affects ALK resistance mutations. J Clin Oncol. 2018;36:1257–9.The manuscript has highlighted clearly the importance of de-tecting and understand the role of the ALK variants and their clinical implications.

    Article  Google Scholar 

  41. Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung Cancer. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology. 2018;36:1199–206. Important manuscript that gave an insight on the resistance mechanism in ALK NSCLC patients.

  42. Drilon A, Wang L, Arcila ME, et al. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clinical Cancer Research : an official journal of the American Association for Cancer Research. 2015;21:3631–9.

    Article  Google Scholar 

  43. Dagogo-Jack I, Brannon AR, Ferris LA, et al. Tracking the evolution of resistance to ALK tyrosine kinase inhibitors through longitudinal analysis of circulating tumor DNA. JCO Precis Oncol. 2018;2018.

  44. Meric-Bernstam F, Brusco L, Shaw K, et al. Feasibility of large-scale genomic testing to facilitate enrollment onto Genomically matched clinical trials. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology. 2015;33:2753–62.

    Article  Google Scholar 

  45. Gainor JF, Dardaei L, Yoda S, et al. Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung Cancer. Cancer Discov. 2016;6:1118–33.

    Article  CAS  Google Scholar 

  46. Bordi P, Tiseo M, Rofi E, et al. Detection of ALK and KRAS mutations in circulating tumor DNA of patients with advanced ALK-positive NSCLC with disease progression during Crizotinib treatment. Clin Lung Cancer. 2017;18:692–7.

    Article  CAS  Google Scholar 

  47. McCoach CE, Blakely CM, Banks KC, et al. Clinical utility of cell-free DNA for the detection of ALK fusions and genomic mechanisms of ALK inhibitor resistance in non-small cell lung Cancer. Clinical Cancer Research : an official journal of the American Association for Cancer Research. 2018;24:2758–70.

    Article  CAS  Google Scholar 

  48. Nilsson RJ, Karachaliou N, Berenguer J, et al. Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer. Oncotarget. 2016;7:1066–75.

    Article  Google Scholar 

  49. Hofman P. ALK status assessment with liquid biopsies of lung Cancer patients. Cancers. 2017;9.

    Article  Google Scholar 

  50. Camidge DR, Theodoro M, Maxson DA, et al. Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (ALK) gene rearrangement, ALK signal copy number, and response to crizotinib therapy in ALK fluorescence in situ hybridization-positive nonsmall cell lung cancer. Cancer. 2012;118:4486–94.

    Article  CAS  Google Scholar 

  51. Cabillic F, Gros A, Dugay F, et al. Parallel FISH and immunohistochemical studies of ALK status in 3244 non-small-cell lung cancers reveal major discordances. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2014;9:295–306.

    Article  CAS  Google Scholar 

  52. Camidge DR, Kono SA, Lu X, et al. Anaplastic lymphoma kinase gene rearrangements in non-small cell lung cancer are associated with prolonged progression-free survival on pemetrexed. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2011;6:774–80.

    Article  Google Scholar 

  53. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385–94.

    Article  CAS  Google Scholar 

  54. Shaw AT, Janne PA, Besse B, et al. Crizotinib vs chemotherapy in ALK+ advanced non-small cell lung cancer (NSCLC): final survival results from PROFILE 1007. J Clin Oncol. 2016;34:9066–6.

    Article  Google Scholar 

  55. Solomon BJ, Mok T, Kim D-W, et al. First-line Crizotinib versus chemotherapy in ALK-positive lung Cancer. N Engl J Med. 2014;371:2167–77.

    Article  Google Scholar 

  56. 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. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology. 2018;36:2251–8.

    Article  CAS  Google Scholar 

  57. 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;8:21903–17.

    Article  Google Scholar 

  58. Huang D, Kim DW, Kotsakis A, et al. Multiplexed deep sequencing analysis of ALK kinase domain identifies resistance mutations in relapsed patients following crizotinib treatment. Genomics. 2013;102:157–62.

    Article  CAS  Google Scholar 

  59. Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clinical Cancer Research : an official journal of the American Association for Cancer Research. 2012;18:1472–82.

    Article  CAS  Google Scholar 

  60. Yoshida T, Oya Y, Tanaka K, et al. Clinical impact of crizotinib on central nervous system progression in ALK-positive non-small lung cancer. Lung Cancer. 2016;97:43–7.

    Article  Google Scholar 

  61. Shaw AT, Kim TM, Crino 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;18:874–86.

    Article  CAS  Google Scholar 

  62. Novello S, Mazieres 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. Annals of Oncology : official journal of the European Society for Medical Oncology. 2018;29:1409–16.

    Article  CAS  Google Scholar 

  63. 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;389:917–29.

    Article  CAS  Google Scholar 

  64. Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017;390:29–39.

    Article  CAS  Google Scholar 

  65. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus Crizotinib in untreated ALK-positive non-small-cell lung Cancer. N Engl J Med. 2017;377:829–38.

    Article  CAS  Google Scholar 

  66. Zhou C, Kim SW, Reungwetwattana T, et al. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. The lancet. Respir Med. 2019;7:437–46.

    CAS  Google Scholar 

  67. Camidge DR, Peters S, Mok T, et al. Updated efficacy and safety data from the global phase III ALEX study of alectinib (ALC) vs crizotinib (CZ) in untreated advanced ALK+ NSCLC. J Clin Oncol. 2018;36:9043–3.

    Article  Google Scholar 

  68. Lin JJ, Zhu VW, Schoenfeld AJ, et al. Brigatinib in patients with Alectinib-refractory ALK-positive NSCLC. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2018;13:1530–8.

    Article  Google Scholar 

  69. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus Crizotinib in ALK-positive non-small-cell lung Cancer. N Engl J Med. 2018;379:2027–39.

    Article  CAS  Google Scholar 

  70. Zou HY, Friboulet L, Kodack DP, et al. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell. 2015;28:70–81. Manuscript that showed the importance to better understand the resistant mechanism to be able to overcome them.

    Article  CAS  Google Scholar 

  71. Shaw AT, Felip E, Bauer TM, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18:1590–9.

    Article  CAS  Google Scholar 

  72. Shaw AT, Solomon BJ, Besse B, et al. ALK Resistance Mutations and efficacy of Lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung Cancer. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology. 2019:JCO1802236.

  73. Gainor JF, Shaw AT, Sequist LV, et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung Cancer: a retrospective analysis. Clinical Cancer Research : an official journal of the American Association for Cancer Research. 2016;22:4585–93.

    Article  CAS  Google Scholar 

  74. Addeo A, Banna GL. PROS: should immunotherapy be incorporated in the treatment of oncogene-driven lung cancer? Transl Lung Cancer Res. 2018;7:S287–9.

    Article  Google Scholar 

  75. Addeo A, Banna GL. PROS: should immunotherapy be incorporated in the treatment of oncogene-driven lung cancer? Transl Lung cancer Res. 2018;7:S283–6.

    Article  CAS  Google Scholar 

  76. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung Cancer. N Engl J Med. 2015;373:1627–39.

    Article  CAS  Google Scholar 

  77. Lee CK, Man J, Lord S, et al. Checkpoint inhibitors in metastatic EGFR-mutated non-small cell lung Cancer-a meta-analysis. Journal of Thoracic Oncology : official publication of the International Association for the Study of Lung Cancer. 2017;12:403–7.

    Article  Google Scholar 

  78. Garassino MC, Cho BC, Kim JH, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018;19:521–36.

    Article  CAS  Google Scholar 

  79. Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378:2288–301.

    Article  CAS  Google Scholar 

  80. Gadgeel SM. Sequencing of ALK inhibitors in ALK+ non-small cell lung Cancer. Curr Treat Options in Oncol. 2017;18:36.

    Article  Google Scholar 

  81. Shaw AT, Solomon BJ, Besse B, et al. ALK resistance mutations and efficacy of Lorlatinib in advanced anaplastic lymphoma kinase-positive non–small-cell lung Cancer. J Clin Oncol. 2019;37:1370–9.

    Article  Google Scholar 

  82. Basler L, Kroeze SG, Guckenberger M. SBRT for oligoprogressive oncogene addicted NSCLC. Lung Cancer. 2017;106:50–7.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Oncology Department, Geneva University Hospital (CH), Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland

    Alex Friedlaender MD & Alfredo Addeo MD

  2. Division of Medical Oncology, Cannizzaro Hospital, Catania, Italy

    Giuseppe Banna MD

  3. Sandip Pravin Patel, UC San Diego Moores Cancer Center, 3855 Health Sciences Dr, La Jolla, CA, 92037, USA

    Sandip Patel MD

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Conflict of Interest

Alex Friedlaender has received compensation from Roche, Pfizer, Astellas and BMS for advisory roles.

Giuseppe Banna declares that he has no conflict of interest.

Sandip Patel has received compensation from AstraZeneca, Bristol-Myers Squibb, Illumina, Nektar Therapeutics, and Tempus for service on advisory boards, and his university receives research funding from Bristol-Myers Squibb, Eli Lilly, Fate Therapeutics, Incyte, AstraZeneca/MedImmune, Merck, Pfizer, Roche/Genentech, Xcovery, Fate Therapeutics, Genocea, and Iovance Biotherapeutics.

Alfredo Addeo has received compensation from Takeda, MSD, BMJ, AstraZeneca, Roche, and Pfizer for service on advisory boards.

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Friedlaender, A., Banna, G., Patel, S. et al. Diagnosis and Treatment of ALK Aberrations in Metastatic NSCLC. Curr. Treat. Options in Oncol. 20, 79 (2019). https://doi.org/10.1007/s11864-019-0675-9

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