Skip to main content
SpringerLink
Log in

Afatinib: First Global Approval

  • R&D Insight Report
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Afatinib, an irreversible inhibitor of the ErbB family of tyrosine kinases, is under development with Boehringer Ingelheim for the once-daily, oral treatment of cancer. Afatinib downregulates ErbB signalling by covalently binding to epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER) 2 and HER4, irreversibly inhibiting tyrosine kinase autophosphorylation. It also inhibits transphosphorylation of HER3. Oral afatinib (Gilotrif™) has been approved in the US for the first-line treatment of patients with metastatic non-small-cell lung cancer (NSCLC) who have tumours with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a US FDA-approved test. Afatinib has also been approved in Taiwan for the first-line treatment of patients with EGFR mutation-positive NSCLC. In addition, the European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of afatinib (Giotrif®) for the treatment of patients with locally advanced or metastatic NSCLC with activating EGFR mutations who are EGFR tyrosine kinase inhibitor naïve. Afatinib is also under regulatory review in Canada, Japan and other Asian countries. This article summarizes the milestones in the development of afatinib, leading to this first approval in patients with metastatic NSCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Metro G, Crino L. The LUX-Lung clinical trial program of afatinib for non-small-cell lung cancer. Expert Rev Anticancer Ther. 2011;11(5):673–82.

    Article  PubMed  CAS  Google Scholar 

  2. Bonanno L, Favaretto A, Rugge M. Role of genotyping in non-small cell lung cancer treatment: current status. Drugs. 2011;71:2231–46.

    Article  PubMed  CAS  Google Scholar 

  3. Liao B-C, Lin C-C, Yang JC-H. First-line management of EGFR-mutated advanced lung adenocarcinoma: recent developments. Drugs. 2013;73(4):357–69.

    Article  PubMed  Google Scholar 

  4. Hirsh V. Afatinib (BIBW 2992) development in non-small-cell lung cancer. Future Oncol. 2011;7(7):817–25.

    Article  PubMed  CAS  Google Scholar 

  5. Chen X, Zhu Q, Zhu L, et al. Clinical perspective of afatinib in non-small cell lung cancer. Lung Cancer. 2013;81(2):155–61.

    Article  PubMed  Google Scholar 

  6. Bordoni RE. Afatinib (BIBW-2992): a novel dual EGFR/HER2neu inhibitor with promising activity in non-small-cell lung cancer. Therapy. 2011;8(1):15–22.

    Article  CAS  Google Scholar 

  7. De Grève J, Teugels E, Geers C, et al. Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012;76(1):123–7.

    Article  PubMed  Google Scholar 

  8. Geuna E, Montemurro F, Aglietta M, et al. Potential of afatinib in the treatment of patients with HER2-positive breast cancer. Breast Can Target Ther. 2012;4:131–7.

    CAS  Google Scholar 

  9. Brockstein BE. Management of recurrent head neck cancer: recent progress and future directions. Drugs. 2011;71:1551–9.

    Article  PubMed  CAS  Google Scholar 

  10. Boehringer Ingelheim Pharmaceuticals Inc. U.S. FDA grants priority review to Boehringer Ingelheim’s afatinib NDA for EGFR mutation-positive advanced NSCLC [media release]. 2013. http://us.boehringer-ingelheim.com. Accessed 25 July 2013.

  11. US Food and Drug Administration. Afatinib. 2013. http://google2.fda.gov/search?q=cache:MSeHvczXMGkJ:www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm360574.htm+afatinib&client=FDAgov&lr=&proxystylesheet=FDAgov&output=xml_no_dtd&ie=UTF-8&site=FDAgov&access=p&oe=ISO-8859-1. Accessed 25 July 2013.

  12. Boehringer Ingelheim Pharmaceuticals Inc. Gilotrif™ (afatinib) tablets, for oral use: US prescribing information. 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201292s000lbl.pdf. Accessed 25 July 2013.

  13. European Medicines Agency. Giotrif (afatinib). 2013. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002280/smops/Positive/human_smop_000570.jsp&mid=WC0b01ac058001d127&source=homeMedSearch&category=human. Accessed 29 July 2013.

  14. Boehringer Ingelheim Pharmaceuticals Inc. ASCO 2013: Boehringer Ingelheim to present data across multiple cancers, including different treatment settings for advanced NSCLC [media release]. 2013. http://www.us.boehringer-ingelheim.com. Accessed 31 July 2013.

  15. Solca F, Dahl G, Zoephel A, et al. Target binding properties and cellular activity of afatinib (BIBW 2992), an irreversible ErbB family blocker. J Pharmacol Exp Ther. 2012;343(2):342–50.

    Article  PubMed  CAS  Google Scholar 

  16. Li D, Ambrogio L, Shimamura T, et al. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008;27(34):4702–11.

    Article  PubMed  CAS  Google Scholar 

  17. Chen G, Kronenberger P, Teugels E, et al. Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab. BMC Med. 2012;10:28.

    Article  PubMed  CAS  Google Scholar 

  18. Ninomiya T, Takigawa N, Ichihara E, et al. Afatinib prolongs survival compared with gefitinib in an epidermal growth factor receptor-driven lung cancer model. Mol Cancer Ther. 2013;12(5):589–97.

    Article  PubMed  CAS  Google Scholar 

  19. Kristeleit H, Puglisi M, Middleton GW, et al. Phase II, open-label trial to assess the effect of continuous oral afatinib (BIBW 2992) at a daily dose of 50 mg on QTc, pharmacokinetics, and efficacy in relapsed or refractory solid tumors including brain metastases and glioblastoma that is not amenable to other therapy [abstract no. 2613]. J Clin Oncol. 2011;29(15 Suppl 1).

  20. Stopfer P, Marzin K, Narjes H, et al. Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers. Cancer Chemother Pharmacol. 2012;69(4):1051–61.

    Article  PubMed  CAS  Google Scholar 

  21. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013. doi:10.1200/JCO.2012.44.2806.

    Google Scholar 

  22. Wu YL, Zhou C, Hu CP, et al. LUX-Lung 6: a randomized, open-label, phase III study of afatinib (A) versus gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lung [abstract no. 8016]. J Clin Oncol. 2013;31(15 Suppl).

  23. Geater SL, Zhou C, Hu CP, et al. LUX-Lung 6: patient-reported outcomes (PROs) from a randomized open-label, phase III study in first-line advanced NSCLC patients (pts) harboring epidermal growth factor receptor (EGFR) mutations [abstract no. 8061]. J Clin Oncol. 2013;31(15 Suppl.).

  24. Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013. doi:10.1200/JCO.2012.46.1764.

    Google Scholar 

  25. Yang JC-H, Shih J-Y, Su W-C, et al. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012;13(5):539–48.

    Article  PubMed  CAS  Google Scholar 

  26. Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012;13(5):528–38.

    Article  PubMed  CAS  Google Scholar 

  27. Hirsh V, Cadranel J, Cong XJ, et al. Symptom and quality of life benefit of afatinib in advanced non-small-cell lung cancer patients previously treated with erlotinib or gefitinib: results of a randomized phase IIb/III trial (LUX-Lung 1). J Thorac Oncol. 2013;8(2):229–37.

    Article  PubMed  CAS  Google Scholar 

  28. Schuler MH, Planchard D, James CHY, et al. Interim analysis of afatinib monotherapy in patients with metastatic NSCLC progressing after chemotherapy and erlotinib/gefitinib (E/G) in a trial of afatinib plus paclitaxel versus investigator’s choice chemotherapy following progression on afatinib monotherapy [abstract no. 7557]. J Clin Oncol. 2012;30(15 Suppl).

  29. De Greve J, Moran T, Graas MP, et al. Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined non-small cell lung cancer (NSCLC) patients [abstract no. 8063]. J Clin Oncol. 2013;31(15 Suppl).

  30. Murakami H, Tamura T, Takahashi T, et al. Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). Cancer Chemother Pharmacol. 2012;69(4):891–9.

    Article  PubMed  CAS  Google Scholar 

  31. Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013. doi:10.1200/JCO.2012.45.0981.

    PubMed  Google Scholar 

  32. Janjigian YY, Smit EF, Horn L, et al. Activity of afatinib/cetuximab in patients (pts) with EGFR mutant non-small cell lung cancer (NSCLC) and acquired resistance (AR) to EGFR inhibitors [abstract no. 12270]. Ann Oncol. 2012;23 Suppl 9:ix401.

    Google Scholar 

  33. Boehringer Ingelheim Inc. Trial of BIBW 2992 (afatinib) + cetuximab in non-small cell lung cancer [ClinicalTrials.gov identifier NCT01090011] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01090011?term=afatinib+cetuximab&rank=2. Accessed 12 Aug 2013.

  34. Boehringer Ingelheim Pharmaceuticals. A phase II trial of afatinib (BIBW 2992) in third-line treatment for patients with stage IIIB/IV adenocarcinoma of the lung harbouring wild-type epidermal growth factor receptor [EGFR] [ClinicalTrials.gov identifier NCT01003899] US National Institutes of Health, ClinicalTrials.gov. 2012. http://www.clinicaltrials.gov/ct2/show/NCT01003899?term=NCT01003899&rank=1. Accessed 2013.

  35. Ahn J-H, Kim S-W, Cho B-C, et al. Phase II trial of afatinib as a third-line treatment for Korean patients with wild-type epidermal growth factor receptor stage IIIb/IV lung adenocarcinoma [poster]. 37th Congress of the European Society for Medical Oncology; 28 Sep–2 Oct 2012; Vienna.

  36. Goss G, Lu S, Felip E, et al. LUX-Lung 8: a randomized, open-label, phase III trial of afatinib vs. erlotinib in patients with advanced squamous cell carcinoma of the lung as second-line therapy following first-line platinum-based chemotherapy [abstract no. 509TiP]. 37th Congress of the European Society for Medical Oncology; 28 Sep–2 Oct 2012; Vienna.

  37. Boehringer Ingelheim Pharmaceuticals. LUX-Lung 8: a phase III trial of afatinib (BIBW 2992) versus erlotinib for the treatment of squamous cell lung cancer after at least one prior platinum based chemotherapy [ClinicalTrials.gov identifier NCT01523587] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01523587?term=NCT01523587&rank=1. Accessed 25 July 2013.

  38. Boehringer Ingelheim Pharmaceuticals. LUX-Lung 7: a phase IIb trial of afatinib (BIBW2992) versus gefitinib for the treatment of 1st line EGFR mutation positive adenocarcinoma of the lung [ClinicalTrials.gov identifier NCT01466660] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01466660?term=NCT01466660&rank=1. Accessed 25 July 2013.

  39. Boehringer Ingelheim Pharmaceuticals. An open label trial of afatinib in treatment-naive (1st line) or chemotherapy pre-treated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutation(s) [ClinicalTrials.gov identifier NCT01853826] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01853826?term=NCT01853826&rank=1. Accessed 25 July 2013.

  40. National Cancer Center Korea. BIBW 2992 plus simvastatin vs. BIBW 2992 in previously treated patients with advanced non-adenocarcinomatous NSCLC [ClinicalTrials.gov identifier NCT01156545] US National Institutes of Health, ClinicalTrials.gov. 2012. http://www.clinicaltrials.gov/ct2/show/NCT01156545?term=NCT01156545&rank=1. Accessed 25 July 2013.

  41. Instituto Nacional de Cancerologia de Mexico. Treatment with BIBW 2992, irreversible inhibitor of EGFR and HER-2 in non small cell lung cancer (NSCLC) [ClinicalTrials.gov identifier NCT01542437] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01542437?term=afatinib&rank=51. Accessed 12 Aug 2013.

  42. Massachusetts General Hospital. Afatinib with CT and RT for EGFR-mutant NSCLC [ClinicalTrials.gov identifier NCT01553942] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01553942?term=afatinib&rank=44. Accessed 12 Aug 2013.

  43. Massachusetts General Hospital. Adjuvant afatinib in stage I-III NSCLC with EGFR mutation [ClinicalTrials.gov identifier NCT01746251] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01746251?term=afatinib&rank=42. Accessed 12 Aug 2013.

  44. Samsung Medical Center. Afatinib plus nimotuzumb for NSCLC [ClinicalTrials.gov identifier NCT01861223] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01861223?term=afatinib&rank=64. Accessed 12 Aug 2013.

  45. Boehringer Ingelheim Inc. Trial of continuous once daily oral treatment using BIBW 2992 (afatinib) plus sirolimus (Rapamune®) in patients with non-small cell lung cancer harbouring an EGFR mutation and/or disease progression following prior erlotinib or gefitinib [ClinicalTrials.gov identifier NCT00993499] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT00993499?term=afatinib&rank=52. Accessed 12 Aug 2013.

  46. Memorial Sloan-Kettering Cancer Center. Afatinib in combination with cisplatin or carboplatin + pemetrexed in patients with EGFR-mutant lung cancers undergoing definitive chemoradiation [ClinicalTrials.gov identifier NCT01836341] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01836341?term=afatinib&rank=18. Accessed 12 Aug 2013.

  47. Boehringer Ingelheim Inc. A study of intermittent, high-dose afatinib to determine the maximal tolerated dose and assess activity of this dose against non-small cell lung cancer with T790M mutations [ClinicalTrials.gov identifier NCT01647711] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01647711?term=afatinib&rank=35. Accessed 12 Aug 2013.

  48. University College London. Efficacy and safety study of BIBW 2992 to treat lung cancer patients (TIMELY) [ClinicalTrials.gov identifier NCT01415011] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01415011?term=afatinib&rank=72. Accessed 12 Aug 2013.

  49. Boehringer Ingelheim Pharmaceuticals. Afatinib expanded access program [ClinicalTrials.gov identifier NCT01649284] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01649284?term=NCT01649284&rank=1. Accessed 25 July 2013.

  50. Schuler M, Awada A, Harter P, et al. A phase II trial to assess efficacy and safety of afatinib in extensively pretreated patients with HER2-negative metastatic breast cancer. Breast Cancer Res Treat. 2012;134(3):1149–59.

    Article  PubMed  CAS  Google Scholar 

  51. Lin NU, Winer EP, Wheatley D, et al. A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab. Breast Cancer Res Treat. 2012;133(3):1057–65.

    Article  PubMed  CAS  Google Scholar 

  52. Gunzer K, De Mont-Serrat H, Uttenreuther-Fischer MM, et al. Addition of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2, to letrozole in estrogen receptor (ER)-positive metastatic breast cancer (mBC) progressing on letrozole monotherapy [abstract no. 1072]. J Clin Oncol. 2010;28(15 Suppl 1): plus poster presented at the 46th Annual Meeting of the American Society of Clinical Oncology; 4–8 Jun 2010; Chicago (IL).

  53. Rimawi MF, Aleixo SB, Rozas AA, et al. A neoadjuvant, randomized, open-label phase II trial of afatinib (A) versus trastuzumab (T) versus lapatinib (L) in patients (pts) with locally advanced HER2-positive breast cancer (BC) [abstract no. 606]. J Clin Oncol. 2012;30(15 Suppl 1).

  54. Xu B, Im SA, Huang CS, et al. LUX-Breast 1: randomized, phase III trial of afatinib (BIBW 2992) and vinorelbine vs. trastuzumab and vinorelbine in patients with HER2-overexpressing metastatic breast cancer (MBC) failing one prior trastuzumab treatment [abstract no. OT1-1-16]. Cancer Res. 2012;72(24 Suppl 3).

  55. Hickish T, Mehta A, Jain M, et al. LUX-Breast 2: phase II, open-label study of oral afatinib in HER2-overexpressing metastatic breast cancer (MBC) patients (PTS) who progressed on prior trastuzumab and/or lapatinib [abstract no. OT1-1-17]. Cancer Res. 2012;72(24 Suppl 3).

  56. Joensuu H, Ould-Kaci M. LUX-Breast 3: randomized phase II trial of afatinib (BIBW 2992) alone or with vinorelbine versus investigator’s choice of treatment in patients (PTS) with HER2-positive breast cancer (BC) with progressive brain metastases after trastuzumab and/or lapatinib-based therapy [abstract no. OT1-1-15]. Cancer Res. 2012;72(24 Suppl 3).

  57. Swanton C, Cromer J. Open-label, phase II trial of afatinib, with or without vinorelbine (V), for the treatment of HER2-overexpressing inflammatory breast cancer (IBC) [abstract no. TPS650]. J Clin Oncol. 2012;30(15 Suppl 1).

  58. Hanusch C, Schneeweiss A, Untch M, et al. Dual blockade with afatinib and trastuzumab as neooadjuvant treatment for patients with locally advanced or operable breast cancer receiving taxane-anthracycline containing chemotherapy (DAFNE)-GBG70 [abstract no. OT1-1-13]. Cancer Res. 2012;72(24 Suppl 3).

  59. Boehringer Ingelheim Inc. Phase I open label trial to assess safety of BIBW 2992 (afatinib) in combination with Herceptin® in patients with HER2-positive advanced breast cancer [ClinicalTrials.gov identifier NCT00950742] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT00950742?term=NCT00950742&rank=1. Accessed 12 Aug 2013.

  60. Cohen EEW, Fayette J, Cupissol D, et al. A randomized, open-label, phase II study of afatinib (BIBW 2992) versus cetuximab in recurrent or metastatic squamous cell carcinoma of the head and neck: final data [abstract no. PP101]. Eur Arch Otorhinolaryngol. 2012;269(4):1374.

    Google Scholar 

  61. Machiels JPH, Licitra LF, Haddad RI, et al. LUX-Head and Neck 1: a phase III, randomized trial of afatinib versus methotrexate (MTX) in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy [abstract no. TPS5598]. J Clin Oncol. 2012;30(15 Suppl 1).

  62. Burtness B, Bourhis J, Vermorken JB, et al. LUX-Head and Neck 2: a randomized, double-blind, placebo-controlled, phase III study of afatinib as adjuvant therapy after chemoradiation in primarily unresected, clinically high-risk, head and neck cancer patients [abstract no. TPS5599]. J Clin Oncol. 2012;30(15 Suppl 1).

  63. Boehringer Ingelheim Pharmaceuticals. LUX-Head and Neck 3: afatinib (BIBW2992) versus methotrexate for the treatment of recurrent and/or metastatic head and neck squamous cell cancer after platinum based chemotherapy [ClinicalTrials.gov identifier NCT01856478] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01856478?term=NCT01856478&rank=1. Accessed 26 July 2013.

  64. Janjigian YY, Ilson D, Kelsen DP, et al. A phase II study of afatinib (BIBW 2992) in patients with advanced HER2-positive trastuzumab-refractory esophagogastric cancer [abstract no. e15017]. J Clin Oncol. 2012;30(15 Suppl 1).

  65. Eisenstat DD, Nabors LB, Mason WP, et al. A phase II study of daily afatinib (BIBW 2992) with or without temozolomide (21/28 days) in the treatment of patients with recurrent glioblastoma [abstract no. 2010]. J Clin Oncol. 2011;29(15 Suppl 1).

  66. Bouche O, Maindrault-Goebel F, Ducreux M, et al. Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for advanced colorectal cancer. Anticancer Res. 2011;31(6):2271–81.

    PubMed  CAS  Google Scholar 

  67. Molife R, De Bono JS, Bell S. A phase II trial to compare BIBF 1120 or BIBW 2992 monotherapy versus a combination of sequential administration of both medications in patients with hormone refractory prostate cancer [abstract no. 203]. 2009 Genitourinary Cancers Symposium; 26–28 Feb 2009; Orlando (FL).

  68. Memorial Sloan-Kettering Cancer Center. Afatinib (BIBW 2992) in patients with advanced HER2-positive trastuzumab-refractory advanced esophagogastric cancer [ClinicalTrials.gov identifier NCT01522768] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01522768?term=afatinib+AND+gastric&rank=2. Accessed 29 July 2013.

  69. Boehringer Ingelheim Pharmaceuticals. BIBW 2992 (afatinib) with or without daily temozolomide in the treatment of patients with recurrent malignant glioma [ClinicalTrials.gov identifier NCT00727506] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT00727506?term=NCT00727506&rank=1. Accessed 29 July 2013.

  70. Boehringer Ingelheim Pharmaceuticals. A multi-centre 3-arm randomised phase II trial of BIBF 1120 versus BIBW 2992 versus sequential administration of BIBF 1120 and BIBW 2992 in patients with hormone-resistant prostate cancer [ClinicalTrials.gov identifier NCT00706628] US National Institutes of Health, ClinicalTrials.gov. 2009. http://www.clinicaltrials.gov/ct2/show/NCT00706628?term=NCT00706628&rank=1. Accessed 29 July 2013.

  71. Boehringer Ingelheim Pharmaceuticals. Open label trial to explore safety of combining afatinib (BIBW 2992) and radiotherapy with or without temozolomide in newly diagnosed glioblastoma multiform [ClinicalTrials.gov identifier NCT00977431] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT00977431?term=NCT00977431&rank=1. Accessed 29 July 2013.

  72. Hellenic Cooperative Oncology Group. Clinical trial of chemotherapy combination cisplatin-fluorouracil-afatinib in patients with inoperable gastric cancer (A-GAPP) [ClinicalTrials.gov identifier NCT01743365] US National Institutes of Health, ClinicalTrials.gov. 2013. http://www.clinicaltrials.gov/ct2/show/NCT01743365?term=afatinib+AND+gastric&rank=1. Accessed 29 July 2013.

  73. Gordon MS, Mendelson DS, Gross M, et al. A Phase I, open-label, dose-escalation study of continuous once-daily oral treatment with afatinib in patients with advanced solid tumors. Invest New Drugs. 2013;31(2):409–16.

    Article  PubMed  CAS  Google Scholar 

  74. Yap TA, Vidal L, Adam J, et al. Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors. J Clin Oncol. 2010;28(25):3965–72.

    Article  PubMed  CAS  Google Scholar 

  75. Marshall J, Hwang J, Eskens FALM, et al. A phase I, open-label, dose escalation study of afatinib, in a 3-week-on/1-week-off schedule in patients with advanced solid tumors. Invest New Drugs. 2013;31(2):399–408.

    Article  PubMed  CAS  Google Scholar 

  76. Eskens FALM, Mom CH, Planting AST, et al. A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours. Br J Cancer. 2008;98(1):80–5.

    Article  PubMed  CAS  Google Scholar 

  77. Awada AH, Dumez H, Hendlisz A, et al. Phase I study of pulsatile 3-day administration of afatinib (BIBW 2992) in combination with docetaxel in advanced solid tumors. Invest New Drugs. 2013;31(3):734–41.

    Article  PubMed  CAS  Google Scholar 

  78. Marshall J, Shapiro GI, Uttenreuther-Fischer M, et al. Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer. Future Oncol. 2013;9(2):271–81.

    Article  PubMed  CAS  Google Scholar 

  79. Vermorken JB, Rottey S, Ehrnrooth E, et al. A phase Ib, open-label study to assess the safety of continuous oral treatment with afatinib in combination with two chemotherapy regimens: cisplatin plus paclitaxel and cisplatin plus 5-fluorouracil, in patients with advanced solid tumors. Ann Oncol. 2013;24(5):1392–400.

    Article  PubMed  CAS  Google Scholar 

  80. Zanetta S, Bennouna J, Isambert N, et al. Phase I safety and tolerability of once daily oral afatinib (A) in combination with gemcitabine (G) in patients with advanced solid tumors [abstract no. e13009]. J Clin Oncol. 2012;30(15 Suppl 1).

  81. Hollebecque A, Bahleda R, Berge Y, et al. Phase I trial to assess the safety and pharmacokinetics of afatinib and weekly vinorelbine in patients with advanced solid tumors [abstract no. 3104]. J Clin Oncol. 2012;30(15 Suppl 1).

  82. Chu QS, Sangha RS, Hotte SJ, et al. A phase I, dose-escalation trial of continuous and pulsed-dose afatinib (A) combined with pemetrexed (P) in patients (pts) with advanced solid tumors: final analysis [abstract no. 2523]. J Clin Oncol. 2013;31(15 Suppl 1).

  83. QIAGEN N.V. QIAGEN receives FDA approval for therascreen® EGFR RGQ PCR Kit as a companion diagnostic for lung cancer patients [media release]. 2013. http://www.qiagen.com/About-Us/Press-Releases/PressReleaseView/?PressReleaseID=418&lang=EN. Accessed 29 July 2013.

  84. QIAGEN N.V. QIAGEN submits companion diagnostic to FDA to guide treatment decisions for new investigational lung cancer compound [media release]. 2013. http://www.qiagen.com. Accessed 31 July 2013.

Download references

Author information

Authors and Affiliations

  1. Adis R & D Insight, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Rosselle T. Dungo

  2. Adis, Auckland, New Zealand

    Gillian M. Keating

Authors
  1. Rosselle T. Dungo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rosselle T. Dungo.

Additional information

This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dungo, R.T., Keating, G.M. Afatinib: First Global Approval. Drugs 73, 1503–1515 (2013). https://doi.org/10.1007/s40265-013-0111-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-013-0111-6

Keywords

Search

Navigation