Drugs

, Volume 73, Issue 18, pp 2031–2051 | Cite as

Crizotinib: A Review of Its Use in the Treatment of Anaplastic Lymphoma Kinase-Positive, Advanced Non-Small Cell Lung Cancer

Adis Drug Evaluation

Abstract

Crizotinib (Xalkori®) is an orally active, small molecule inhibitor of multiple receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK), c-Met/hepatocyte growth factor receptor and c-ros oncogene 1. In the EU, crizotinib has been conditionally approved for the treatment of adults with previously treated, ALK-positive, advanced non-small cell lung cancer (NSCLC). This approval has been based on objective response rate and tolerability data from two ongoing phase I/II studies (PROFILE 1001 and PROFILE 1005); these results have been substantiated and extended by findings from an ongoing phase III study (PROFILE 1007) in patients with ALK-positive, advanced NSCLC who had received one prior platinum-based regimen. Those treated with crizotinib experienced significant improvements in progression-free survival, objective response rate, lung cancer symptoms and global quality of life, as compared with those treated with standard second-line chemotherapy (pemetrexed or docetaxel). The relative survival benefit with crizotinib is unclear, however, as the data are still immature and likely to be confounded by the high cross-over rate among chemotherapy recipients. Crizotinib treatment was generally well tolerated in the three PROFILE studies, with liver transaminase elevations and neutropenia being the most common grade 3 or 4 adverse events. Crizotinib is the standard of care in terms of the treatment of patients with ALK-positive, advanced NSCLC; while the current EU approval is for second (or subsequent)-line use only, the first-line use of the drug is being evaluated in ongoing phase III studies. Key issues relating to the use of crizotinib in clinical practice include identifying the small subset of eligible patients, the almost inevitable development of resistance and the high cost of treatment.

References

  1. 1.
    International Agency for Research on Cancer. GLOBOCAN 2008: estimated cancer incidence, mortality, prevalence and disability-adjusted life years (DALYs) worldwide in 2008. http://globocan.iarc.fr/. Accessed 31 Jul 2013.
  2. 2.
    D’Addario G, Fruh M, Reck M, et al. Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl 5):v116–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Ozkaya S, Findik S, Dirican A, et al. Long-term survival rates of patients with stage IIIB and IV non-small cell lung cancer treated with cisplatin plus vinorelbine or gemcitabine. Exp Ther Med. 2012;4(6):1035–8.PubMedGoogle Scholar
  4. 4.
    Bonanno L, Favaretto A, Rugge M, et al. Role of genotyping in non-small cell lung cancer treatment: current status. Drugs. 2011;71(17):2231–46.PubMedCrossRefGoogle Scholar
  5. 5.
    Felip E, Cedres S, Checa E, et al. How to integrate current knowledge in selecting patients for first line in NSCLC? Ann Oncol. 2010;21(Suppl 7):vii230–3.Google Scholar
  6. 6.
    Larsen JE, Cascone T, Gerber DE, et al. Targeted therapies for lung cancer: clinical experience and novel agents. Cancer J. 2011;17(6):512–27.PubMedCrossRefGoogle Scholar
  7. 7.
    Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12(2):175–80.PubMedCrossRefGoogle Scholar
  8. 8.
    Thomas R, Wolf J. Personalized therapy of lung cancer. Onkologie. 2012;35(Suppl 1):14–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Vadakara J, Borghaei H. Personalized medicine and treatment approaches in non-small-cell lung carcinoma. Pharmgenomics Pers Med. 2012;5:113–23.PubMedGoogle Scholar
  10. 10.
    Villaruz LC, Socinski MA. Personalized therapy for non-small cell lung cancer: which drug for which patient? Semin Thorac Cardiovasc Surg. 2011;23(4):281–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Vincent MD, Kuruvilla MS, Leighl NB, et al. Biomarkers that currently affect clinical practice: EGFR, ALK, MET. KRAS. Curr Oncol. 2012;19(Suppl 1):S33–44.Google Scholar
  12. 12.
    Rafael Sierra J, Tsao M-S. c-MET as a potential therapeutic target and biomarker in cancer. Ther Adv Med Oncol. 2011;3(Suppl 1):S21–S35.Google Scholar
  13. 13.
    Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703.PubMedCrossRefGoogle Scholar
  14. 14.
    Cardarella S, Ogino A, Nishino M, et al. Clinical, pathological and biological features associated with BRAF mutations in non-small cell lung cancer. Clin Cancer Res. 2013;19(16):4532–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Peters S, Michielin O, Zimmermann S. Dramatic response induced by vemurafenib in a BRAF V600E-mutated lung adenocarcinoma. J Clin Oncol. 2013;31(20):e341–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Mazières J, Peters S, Lepage B, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol. 2013;31(16):1997–2003.PubMedCrossRefGoogle Scholar
  17. 17.
    Lipson D, Capelletti M, Yelensky R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012;18(3):382–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Bergethon K, Shaw AT, Ou SHI, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8):863–70.PubMedCrossRefGoogle Scholar
  19. 19.
    Davies KD, Le AT, Theodoro MF, et al. Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. Clin Cancer Res. 2012;18(17):4570–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Minoo P, Wang H-Y. ALK-immunoreactive neoplasms. Int J Clin Exp Pathol. 2012;5(5):397–410.PubMedGoogle Scholar
  21. 21.
    Chiarle R, Voena C, Ambrogio C, et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008;8(1):11–23.PubMedCrossRefGoogle Scholar
  22. 22.
    Curran MP. Crizotinib: in locally advanced or metastatic non-small cell lung cancer. Drugs. 2012;72(1):99–107.PubMedCrossRefGoogle Scholar
  23. 23.
    Ou SHI. Crizotinib: a novel and first-in-class multitargeted tyrosine kinase inhibitor for the treatment of anaplastic lymphoma kinase rearranged non-small cell lung cancer and beyond. Drug Des Devel Ther. 2011;5:471–85.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee JA, Bubendorf L, Stahel RA, et al. Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives. Expert Rev Anticancer Ther. 2013;13(5):625–36.PubMedCrossRefGoogle Scholar
  25. 25.
    Pfizer Limited. Xalkori 200 mg hard capsules: EU summary of product characteristics. 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002489/WC500134759.pdf. Accessed 3 Jul 2013.
  26. 26.
    Zou HY, Li Q, Lee J, et al. Antitumor efficacy of crizotinib (PF-02341066), a potent and selective ALK and c-Met RTK inhibitor, in EML4-ALK driven NSCLC tumors in vitro and in vivo [abstract no. LB-390]. 102nd Annual Meeting of the American Association for Cancer Research; 2–6 Apr 2011; Orlando (FL).Google Scholar
  27. 27.
    Zou HY, Li Q, Lee JH, et al. An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms. Cancer Res. 2007;67(9):4408–17.PubMedCrossRefGoogle Scholar
  28. 28.
    Sun Y, Nowak KA, Zaorsky NG, et al. ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK. Mol Cancer Ther. 2013;12(5):696–704.PubMedCrossRefGoogle Scholar
  29. 29.
    Yasuda H, de Figueiredo-Pontes LL, Kobayashi S, et al. Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer. J Thorac Oncol. 2012;7(7):1086–90.PubMedCrossRefGoogle Scholar
  30. 30.
    Tanizaki J, Okamoto I, Okamoto K, et al. MET tyrosine kinase inhibitor crizotinib (PF-02341066) shows differential antitumor effects in non-small cell lung cancer according to MET alterations. J Thorac Oncol. 2011;6(10):1624–31.PubMedCrossRefGoogle Scholar
  31. 31.
    Ou SHI, Tan J, Yen Y, et al. ROS1 as a ‘druggable’ receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway. Expert Rev Anticancer Ther. 2012;12(4):447–56.PubMedCrossRefGoogle Scholar
  32. 32.
    Bang YJ. The potential for crizotinib in non-small cell lung cancer: a perspective review. Ther Adv Med Oncol. 2011;3(6):279–91.PubMedCrossRefGoogle Scholar
  33. 33.
    Christensen JG, Zou HY, Arango ME, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther. 2007;6(12 Pt. 1):3314–22.Google Scholar
  34. 34.
    Yamazaki S, Vicini P, Shen Z, et al. Pharmacokinetic/pharmacodynamic modeling of crizotinib for anaplastic lymphoma kinase inhibition and antitumor efficacy in human tumor xenograft mouse models. J Pharmacol Exp Ther. 2012;340(3):549–57.PubMedCrossRefGoogle Scholar
  35. 35.
    Tumati V, Kumar S, Yu L, et al. Effect of PF-02341066 and radiation on non-small cell lung cancer cells. Oncol Rep. 2013;29(3):1094–100.PubMedGoogle Scholar
  36. 36.
    Li C, Alvey C, Bello A, et al. Pharmacokinetics (PK) of crizotinib (PF-02341066) in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors. J Clin Oncol. 2011;29(Suppl; abstract no. e13065).Google Scholar
  37. 37.
    Johnson TR, Goulet L, Smith EB, et al. Metabolism, excretion and pharmacokinetics of [14C]crizotinib following oral administration to healthy subjects [abstract no. P83]. Drug Metab Rev. 2011;43:77.Google Scholar
  38. 38.
    Pfizer Inc. XALKORI® (crizotinib) capsules, oral. US prescribing information. 2013. http://labeling.pfizer.com/showlabeling.aspx?id=676. Accessed 3 Jul 2013.
  39. 39.
    Costa DB, Kobayashi S, Pandya SS, et al. CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib. J Clin Oncol. 2011;29(15):e443–5.PubMedCrossRefGoogle Scholar
  40. 40.
    Tan W, Wilner KD, Bang YJ, et al. Pharmacokinetics of PF-02341066, a dual ALK/MET inhibitor after multiple oral doses to advanced cancer patients. J Clin Oncol. 2010;28 (Suppl; abstract no. 2596).Google Scholar
  41. 41.
    Wang E, Nickens D, Bello A, et al. Clinical implication of a population pharmacokinetic analysis of XALKORI (crizotinib) in 1,182 patients with non-small cell lung cancer (NSCLC) and 32 patients with other solid tumors [abstract no. MO07.04 plus oral presentation]. International Association for the Study of Lung Cancer, 15th World Conference on Lung Cancer; 27–30 Oct 2013; Sydney.Google Scholar
  42. 42.
    Nishio M, Hirsh V, Kim D-W, et al. Efficacy, safety, and patient-reported outcomes (PROs) with crizotinib versus chemotherapy in Asian patients in a phase III study of previously treated advanced ALK-positive non-small cell lung cancer (NSCLC) [abstract no. O16.05 plus oral presentation]. International Association for the Study of Lung Cancer, 15th World Conference on Lung Cancer; 27–30 Oct 2013; Sydney.Google Scholar
  43. 43.
    Hirsh V, Blackhall FH, Kim D-W, et al. Impact of crizotinib on patient-reported symptoms and quality of life (QOL) compared with single-agent chemotherapy in a phase III study of advanced ALK + non-small cell lung cancer. J Clin Oncol. 2013;31(Suppl; abstract no. 8108).Google Scholar
  44. 44.
    Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94.PubMedCrossRefGoogle Scholar
  45. 45.
    Pfizer Limited. An investigational drug, PF-02341066 is being studied versus standard of care in patients with advanced non-small cell lung cancer with a specific gene profile involving the anaplastic lymphoma kinase (ALK) gene [ClinicalTrials.gov identifier NCT00932893]. US National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/ct2/show/results/NCT00932893. Accessed 3 Jul 2013.
  46. 46.
    European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP). CHMP assessment report: Xalkori. International non-proprietary name: crizotinib. Procedure no. EMEA/H/C/002489. 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002489/WC500134761.pdf. Accessed 3 Jul 2013.
  47. 47.
    Hida T, Shi Y, Ahn MJ, et al. Exploratory subgroup analysis of crizotinib efficacy and safety in Asian and non-Asian patients with advanced ALK-positive non-small cell lung cancer (NSCLC) enrolled in a global phase II study [abstract]. J Thorac Oncol. 2012;7(11 Suppl 5):S454–5.Google Scholar
  48. 48.
    Schnell P, Safferman AZ, Bartlett CH, et al. Clinical presentation of hepatotoxicity-associated crizotinib in ALK-positive (ALK+) advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2012;30(Suppl; abstract no. 7598).Google Scholar
  49. 49.
    Salgia R, Solomon BJ, Shaw AT, et al. Visual effects in anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) patients treated with crizotinib. J Clin Oncol. 2012;30(Suppl; abstract no. 7596).Google Scholar
  50. 50.
    Ou SHI, Tong WP, Azada M, et al. Heart rate decrease during crizotinib treatment and potential correlation to clinical response. Cancer. 2013;119:1969–75.PubMedCrossRefGoogle Scholar
  51. 51.
    Weickhardt AJ, Rothman MS, Salian-Mehta S, et al. Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012;118(21):5302–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Weickhardt AJ, Doebele RC, Purcell WT, et al. Symptomatic reduction in free testosterone levels secondary to crizotinib use in male cancer patients. Cancer. 2013;119(30):2383–90.PubMedCrossRefGoogle Scholar
  53. 53.
    Shaw AT, Solomon BJ, Mok T, et al. Effect of treatment duration on incidence of adverse events (AEs) in a phase III study of crizotinib versus chemotherapy in advanced ALK-positive non-small cell lung cancer (NSCLC) [abstract no. P2.11-041 plus poster]. International Association for the Study of Lung Cancer, 15th World Conference on Lung Cancer; 27–30 Oct 2013; Sydney.Google Scholar
  54. 54.
    Nelson R. Crizotinib receives conditional marketing approval in Europe. 2012. http://www.medscape.com/viewarticle/773280. Accessed 22 Aug 2013.
  55. 55.
    Novartis International AG. Novartis breakthrough therapy LDK378 shows a marked clinical response in patients with ALK+ non-small cell lung cancer [media release]. 3 June 2013. http://hugin.info/134323/R/1706664/565008.pdf.
  56. 56.
    Seto T, Kiura K, Nishio M, et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study. Lancet Oncol. 2013;14:590–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Nakagawa K, Kiura K, Nishio M, et al. A phase I/II study with a highly selective ALK inhibitor CH5424802 in ALK-positive non-small cell lung cancer (NSCLC) patients: updated safety and efficacy results from AF-001JP. J Clin Oncol. 2013;31(Suppl; abstract no. 8033).Google Scholar
  58. 58.
    Camidge DR, Bazhenova L, Salgia R, et al. First-in-human dose-finding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies: updated results. J Clin Oncol. 2013;31(Suppl; abstract no. 8031).Google Scholar
  59. 59.
    Socinski MA, Goldman J, El-Hariry I, et al. A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. Clin Cancer Res. 2013;19(11):3068–77.PubMedCrossRefGoogle Scholar
  60. 60.
    Sequist LV, Gettinger S, Senzer NN, et al. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol. 2010;28(33):4953–60.PubMedCrossRefGoogle Scholar
  61. 61.
    Camidge DR, Bang Y-J, Kwak EL, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012;13(10):1011–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Crinò L, Kim D-W, Riely GJ, et al. Initial phase 2 results with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC): PROFILE 1005. Proc Am Soc Clin Oncol 2011;29(Suppl; abstract no. 7514).Google Scholar
  63. 63.
    Shaw AT, Yeap BY, Solomon BJ, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011;12(11):1004–12.PubMedCrossRefGoogle Scholar
  64. 64.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines): non-small cell lung cancer. Version 2. 2013. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 20 Aug 2013.
  65. 65.
    Pfizer. A clinical trial testing the efficacy of crizotinib versus standard chemotherapy pemetrexed plus cisplatin or carboplatin in patients with ALK positive non squamous cancer of the lung (PROFILE 1014) [ClinicalTrials.gov identifier NCT01154140]. US National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/show/NCT01154140. Accessed 19 Aug 2013.
  66. 66.
    Pfizer. A study of crizotinib versus chemotherapy in previously untreated East Asian non-small cell lung cancer patients [ClinicalTrials.gov identifier NCT01639001]. US National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/show/NCT01639001. Accessed 19 Aug 2013.
  67. 67.
    Gainor JF, Varghese AM, Ou SHI, et al. ALK rearrangements are mutually exclusive with mutations in EFGR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res. 2013;19(15):4273–81.PubMedCrossRefGoogle Scholar
  68. 68.
    Shaw A, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non-small cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27(26):4247–53.PubMedCrossRefGoogle Scholar
  69. 69.
    Kris MG, Johnson BE, Kwiatkowski A, et al. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: the NCI’s Lung Cancer Mutation Consortium (LCMC). J Clin Oncol. 2011;29(Suppl; abstract no. CRA7506).Google Scholar
  70. 70.
    Boehringer Ingelheim. Afatinib receives positive CHMP opinion for patients with EGFR mutation positive lung cancer in European Union [media release]. 26 July 2013. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/26_july_2013_oncology.html.
  71. 71.
    GlaxoSmithKline. A phase II study of the selective BRAF kinase inhibitor GSK2118436 in subjects with advanced non-small cell lung cancer and BRAF mutations [ClinicalTrials.gov identifier NCT01336634]. US National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/ct2/show/NCT01336634. Accessed 12 Sep 2013.
  72. 72.
    Roche. Tarceva 25 mg film-coated tablets. EU summary of product characteristics. 2010. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000618/WC500033994.pdf. Accessed 20 Aug 2013.
  73. 73.
    AstraZeneca AB. IRESSA 250 mg film-coated tablets. EU summary of product characteristics. 2009. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001016/WC500036358.pdf. Accessed 20 Aug 2013.
  74. 74.
    Boehringer Ingelheim. LUME-Lung 1: nintedanib plus chemotherapy extends the life of lung cancer patients with adenocarcinoma [media release]. 3 June 2013. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/03_june_2013_oncology.html.
  75. 75.
    Janne PA, Shaw AT, Pereira JR, et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomized, multicentre, placebo-controlled, phase 2 study. Lancet Oncol. 2013;14(1):38–47.PubMedCrossRefGoogle Scholar
  76. 76.
    Metro G, Minotti V, Crino L. Years of sorafenib investigation in advanced non-small cell lung cancer: is there a ‘NExUS’ linking an unsuccessful treatment and a potentially active one? J Thorac Dis. 2012;4(6):635–8.PubMedGoogle Scholar
  77. 77.
    European Society for Medical Oncology. ESMO 2012 press release: phase III MISSION trial. Sorafenib does not extend overall survival as third or fourth line therapy in lung cancer, EGFR status may help select patients who will benefit most. http://www.esmo.org/Conferences/Past-Conferences/ESMO-2012-Congress/News-Press-Releases/ESMO-2012-Press-Releases/Phase-III-MISSION-trial. Accessed 20 Aug 2013.
  78. 78.
    ArQule Inc. ArQule and Daiichi Sankyo announce discontinuation of phase 3 MARQUEE clinical trial in non-small cell lung cancer [media release]. 2 October 2012. http://investors.arqule.com/releasedetail.cfm?ReleaseID=710618.
  79. 79.
    Platt A, Elvin P, Morten J, et al. Retrospective evaluation of RET biomarker status and outcome to vandetanib in four phase III randomized NSCLC trials. J Clin Oncol. 2013;31 (Suppl; abstract no. 8045).Google Scholar
  80. 80.
    Langer CJ, Mok T, Postmus PE. Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). Cancer Treat Rev. 2013;39(3):252–60.PubMedCrossRefGoogle Scholar
  81. 81.
    Roche. Avastin 25 mg/ml concentrate for solution for infusion. EU summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000582/WC500029271.pdf. Accessed 20 Aug 2013.
  82. 82.
    Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomized phase III trial. Lancet. 2009;373(9764):1525–31.PubMedCrossRefGoogle Scholar
  83. 83.
    European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP). Assessment report for erbitux. International non-proprietary name/common name: cetuximab. Procedure no. EMEA/H/C/558/II/0029. 2010. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000558/WC500075683.pdf. Accessed 20 Aug 2013.
  84. 84.
    European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP). Merck KGaA withdraws its application for an extension of the indication for Erbitux (cetuximab) [press release] 19 Sep 2012. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000558/wapp/Post-authorisation/human_wapp_000145.jsp&mid=WC0b01ac058001d128.
  85. 85.
    Eli Lilly and Company. Lilly announces phase III necitumumab study meets primary endpoint of overall survival [media release]. 13 Aug 2013. http://newsroom.lilly.com/releasedetail.cfm?releaseid=784772.
  86. 86.
    Eli Lilly and Company. Lilly releases phase II results for monoclonal antibody ramucirumab in lung cancer [media release]. 29 September 2012. http://newsroom.lilly.com/releasedetail.cfm?releaseid=710172.
  87. 87.
    Eli Lilly and Company. A study of chemotherapy and ramucirumab vs. chemotherapy alone in second line non-small cell lung cancer participants who received prior first line platinum based chemotherapy [ClinicalTrials.gov identifier NCT01168973]. US National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/show/NCT01168973. Accessed 20 Aug 2013.
  88. 88.
    Villaflor VM, Salgia R. Targeted agents in non-small cell lung cancer therapy: what is there on the horizon? J Carcinog. 2013;12:7. Available from: http://www.carcinogenesis.com/text.asp?2013/12/1/7/109253.
  89. 89.
    Casaluce F, Sgambato A, Maione P, et al. ALK inhibitors: a new targeted therapy in the treatment of advanced NSCLC. Target Oncol. 2013;8(1):55–67.PubMedCrossRefGoogle Scholar
  90. 90.
    Yi ES, Chung J-H, Kulig K, et al. Detection of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer and related issues in ALK inhibitor therapy: a literature review. Mol Diagn Ther. 2012;16(3):143–50.PubMedGoogle Scholar
  91. 91.
    Shaw AT, Solomon B, Kenudson MM. Crizotinib and testing for ALK. J Natl Compr Canc Netw. 2011;9(12):1335–41.PubMedGoogle Scholar
  92. 92.
    Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. J Thorac Oncol. 2013;8(7):823–59.PubMedCrossRefGoogle Scholar
  93. 93.
    Thunnissen E, Bubendorf L, Dietel M, et al. EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch. 2012;461(3):245–57.PubMedCrossRefGoogle Scholar
  94. 94.
    Atherly AJ, Camidge DR. The cost-effectiveness of screening lung cancer patients for targeted drug sensitivity markers. Br J Cancer. 2012;106(6):1100–6.PubMedCrossRefGoogle Scholar
  95. 95.
    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(8):1467–77.PubMedCrossRefGoogle Scholar
  96. 96.
    Conklin CMJ, Craddock KJ, Have C, et al. Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent. J Thorac Oncol. 2013;8:45–51.PubMedCrossRefGoogle Scholar
  97. 97.
    Martinez P, Hernandez-Losa J, Montero MA, et al. Fluourescent in situ hybridization and immunohistochemistry as diagnostic methods for ALK positive non-small cell lung cancer patients. PLoS ONE. 2013;8(1):e52261. doi:10.1371/journal.pone.0052261.PubMedCrossRefGoogle Scholar
  98. 98.
    Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012;18(5):1472–82.PubMedCrossRefGoogle Scholar
  99. 99.
    Voena C, Chiarle R. The battle against ALK resistance: successes and setbacks. Expert Opin Investig Drugs. 2012;21(12):1751–4.PubMedCrossRefGoogle Scholar
  100. 100.
    Sasaki T, Janne PA. New strategies for treatment of ALK-rearranged non-small cell lung cancers. Clin Cancer Res. 2011;17(23):7213–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Otterson GA, Riely GJ, Shaw AT, et al. Clinical characteristics of ALK + NSCLC patients (pts) treated with crizotinib beyond disease progression (PD): potential implications for management. J Clin Oncol. 2012;30(Suppl; abstract no. 7600).Google Scholar
  102. 102.
    Ou SHI, Zhou C, Ahn MJ, et al. Treatment of ALK-positive non-small cell lung cancer patients with crizotinib beyond disease progression: Clinical assessment and potential management implications [abstract]. J Thorac Oncol. 2012;7(11 Suppl 5):S446.Google Scholar
  103. 103.
    Crino L, Ahn MJ, Ou SHI, et al. Clinical experience with crizotinib in patients with advanced ALK-positive non-small cell lung cancer and brain metastases [abstract 3413 plus poster]. European Cancer Congress 2013; 27 Sep–1 Oct 2013; Amsterdam.Google Scholar
  104. 104.
    Choi YL, Soda M, Yamashita Y, et al. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med. 2010;363:1734–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Sasaki T, Koivunen J, Ogino A, et al. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 2011;71(18):6051–60.PubMedCrossRefGoogle Scholar
  106. 106.
    Doebele RC, Aisner DL, Le AT, et al. Analysis of resistance mechanisms to ALK kinase inhibitors in ALK+ NSCLC patients. J Clin Oncol. 2012;30(Suppl; abstract no. 7504).Google Scholar
  107. 107.
    Tanizaki J, Okamoto I, Okabe T, et al. Activation of HER family signaling as a mechanism of acquired resistance to ALK inhibitors in EML4-ALK-positive non-small cell lung cancer. Clin Cancer Res. 2012;18(22):6219–26.PubMedCrossRefGoogle Scholar
  108. 108.
    Ou SHI, Riely GJ, Tang Y, et al. Clinical benefit of continuing crizotinib beyond initial disease progression in patients with advanced ALK-positive non-small-cell lung cancer [abstract no. MO07.01 plus oral presentation]. International Association for the Study of Lung Cancer, 15th World Conference on Lung Cancer; 27–30 Oct 2013; Sydney.Google Scholar
  109. 109.
    Shaw AT, Solomon B. Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer. 2013. http://www.uptodate.com/contents/anaplastic-lymphoma-kinase-alk-fusion-oncogene-positive-non-small-cell-lung-cancer#H4. Accessed 19 Aug 2013.
  110. 110.
    Takeda M, Okamoto I, Nakagawa K. Clinical impact of continued crizotinib administration after isolated central nervous system progression in patients with lung cancer positive for ALK rearrangement. J Thorac Oncol. 2013;8(5):654–7.PubMedCrossRefGoogle Scholar
  111. 111.
    Matsuoka H, Kurata T, Okamoto I, et al. Clinical response to crizotinib retreatment after acquisition of drug resistance. J Clin Oncol. 2013;31(19):e322–3.PubMedCrossRefGoogle Scholar
  112. 112.
    Weickhardt AJ, Scheier B, Burke JM, et al. Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer. J Thorac Oncol. 2012;7(12):1807–14.PubMedCrossRefGoogle Scholar
  113. 113.
    Becker A, Crombag L, Heideman DA, et al. Retreatment with erlotinib: regain of TKI sensitivity following a drug holiday for patients with NSCLC who initially responded to EGFR-TKI treatment. Eur J Cancer. 2011;47(17):2603–6.PubMedCrossRefGoogle Scholar
  114. 114.
    Data on file, Pfizer Inc., 2013.Google Scholar
  115. 115.
    van de Vooren K, Curto A, Garattini L. Optional copayments on anti-cancer drugs. BMJ. 2013;346:f349.PubMedCrossRefGoogle Scholar
  116. 116.
    National Institute for Health and Care Excellence. Final appraisal determination: crizotinib for previously treated non-small cell lung cancer associated with an anaplastic lymphoma kinase fusion gene. 2013. http://www.nice.org.uk/nicemedia/live/13639/64900/64900.pdf. Accessed 21 Aug 2013.
  117. 117.
    National Institute for Health and Care Excellence. NICE consults on new draft recommendations for lung cancer drug [press release]. 26 March 2013. http://www.nice.org.uk/newsroom/pressreleases/CrizotinibACD.jsp. 2013.
  118. 118.
    Ou SHI, Kim D-W, Camidge DR, et al. Crizotinib therapy for patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC) [abstract no. MO07.03 plus oral presentation]. International Association for the Study of Lung Cancer, 15th World Conference on Lung Cancer; 27–30 Oct 2013; Sydney.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.AdisNorth ShoreNew Zealand

Personalised recommendations