Drug insight: Intracellular inhibitors of HER2-clinical development of lapatinib in breast cancer

Nature Clinical Practice Oncology

Volumn 5, Issue 9, 2008, Pages 512-520

  Cameron, David A ^a   Stein, Steven ^b  

^a NCRN Co ordinating Centre   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTHRACYCLINE DERIVATIVE; CAPECITABINE; CYCLOPHOSPHAMIDE; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIRUBICIN; ERLOTINIB; FLUOROURACIL; FULVESTRANT; GEFITINIB; LAPATINIB; LETROZOLE; PACLITAXEL; PLACEBO; TAMOXIFEN; TAXANE DERIVATIVE; TRASTUZUMAB;

ABDOMINAL PAIN; ADJUVANT THERAPY; ANOREXIA; BLOATING; BLOOD BRAIN BARRIER; BREAST CANCER; CANCER HORMONE THERAPY; CANCER RESISTANCE; CARDIOTOXICITY; CENTRAL NERVOUS SYSTEM METASTASIS; CHEMOTHERAPY INDUCED EMESIS; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DIARRHEA; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG POTENTIATION; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FLATULENCE; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL SYMPTOM; HAND FOOT SYNDROME; HEART DISEASE; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; LIVER FUNCTION TEST; LOADING DRUG DOSE; LUNG CANCER; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; OPTIMAL DRUG DOSE; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SOLID TUMOR;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BREAST NEOPLASMS; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DEOXYCYTIDINE; DISEASE PROGRESSION; FEMALE; FLUOROURACIL; GENES, ERBB-2; HUMANS; PACLITAXEL; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTOR, ERBB-2; TAMOXIFEN; TIME FACTORS;

EID: 51149117030     PISSN: 17434254     EISSN: 17434262     Source Type: Journal    
DOI: 10.1038/ncponc1156     Document Type: Review

References (55)

1. Dixon RB et al. (2004) Chapter 33: Cancer of the Breast: Section 1: Molecular Biology of Breast Cancer. In Cancer: Principles and Practice of Oncology, edn 7 (Eds DeVita VT et al.) Philadelphia: Lippincott Williams & Wilkins
2. Linggi B and Carpenter G (2006) ErbB receptors: New insights on mechanisms and biology. Trends Cell Biol 16: 649-656
3. Xia W et al. (2004) Truncated ErbB2 receptor (p95ErbB2) is regulated by heregulin through heterodimer formation with ErbB3 yet remains sensitive to the dual EGFR/ErbB2 kinase inhibitor GW572016. Oncogene 23: 646-653
4. Slamon DJ et al. (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783-792
5. Cobleigh MA et al. (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17: 2639-2648
6. Vogel CL et al. (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20: 719-726
7. Romond EH et al. (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353: 1673-1684
8. Smith I et al. for the HERA study team (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369: 29-36
9. Nahta R et al. (2006) Mechanisms of Disease: Understanding resistance of HER2 therapy in human breast cancer. Nat Clin Pract Oncol 3: 269-280
10. Guarneri V et al. (2006) Long term cardiac tolerability of trastuzumab in metastatic breast cancer: The MD Anderson Cancer Center experience. J Clin Oncol 1: 4107-4115
11. Pugatsch T et al. (2006) Anti-erbB2 treatment induces cardiotoxicity by interfering with cell survival pathways. Breast Cancer Res 8: R35
12. Crone SA et al. (2002) ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 8: 459-465
13. Tykerb® [package insert]. Research Triangle Park, NC: GlaxoSmith Kline; 2007
14. Konecny GE et al. (2006) Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 66: 1630-1639
15. Rusnak DW et al. (2001) The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: Potential therapy for cancer. Cancer Res 61: 7196-7203
16. Rusnak DW et al. (2001) The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther 1: 85-94
17. Nahta R et al. (2007) Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: Effects on insulin-like growth factor I signaling. Mol Cancer Ther 6: 667-674
18. Xia W et al. (2007) Lapatinib antitumor activity is not dependent upon phosphatase and tensin homologue deleted on chromosome 10 in ErbB2-overexpressing breast cancers. Cancer Res 67: 1170-1175
19. Xia W et al. (2005) Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of Erb132-overexpressing breast cancer cells. Oncogene 24: 6213-6221
20. Perez E et al. (2006) Cardiac safety experience in 3558 patients treated with lapatinib [abstract #1420] Ann Oncol 17 (Suppl 9)
21. Bence AK et al. (2005) Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects. Invest New Drugs 23: 39-49
22. Versola M et al. (2004) Clinical activity of GW572016 in EGF1 0003 in patients with solid tumors [abstract #3947]. J Clin Oncol 22 (Suppl)
23. Spector NL et al. (2005) Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies. J Clin Oncol 23: 2502-2512
24. Burris HA et al. (2005) Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. J Clin Oncol 2: 5305-5313
25. Gomez HL et al. (2006) Results from a phase II randomized study of lapatinib as first-line treatment for patients with HER2-amplified locally advanced or metastatic breast cancer. [http://www.posters2view.com/sabcs06/view.php?nu=1090] (accessed 19 June 2007)
26. Blackwell KL et al. (2005) Determining relevant biomarkers from tissue and serum that may predict response to single agent lapatinib in trastuzumab refractory metastatic breast cancer [abstract #3004]. J Clin Oncol 23: 193s
27. Burstein H et al. (2004) A phase II, open-label, multicenter study of lapatinib in two cohorts of patients with advanced or metastatic breast cancer who have progressed while receiving trastuzumab-containing regimens [abstract #1040]. Ann Oncol 15 (Suppi 3): 27
28. Baselga J et al. (2005) Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol 23: 2162-2171
29. Clinicaltnals.gov (online 7 January 2004) Lapatinib in combination with trastuzumab versus lapatinib monotherapy in subjects with metastatic breast cancer [http://clinicaltrials.gov/ct/show/NCT00320385] (accessed 30 April 2007)
30. Clinicaltrials.gov. Paclitaxel with/without GW572016 (Lapatinib) as first line therapy for women with advanced or metastatic breast cancer [http://www.clinicaltrials.gov/ct/show/NCT00075270?order=1] (accessed 26 September 2007)
31. Clinicaltrials.gov. Study in women and men with metastatic breast cancer that have overexpression of ErbB2 [htp://www.clinicaltrials.gov/ct/show/ NCT00281658?order=1] (accessed 26 September 2007)
32. Clinicaltrials.gov. ErbB2 over-expressing metastatic breast cancer study using paclitaxel, trastuzumab, and lapatinib [http://www.clinicaltrials.gov/ct/show/NCT00272987?order=1] (accessed 26 September 2007)
33. Clinicaltrials.gov. Study comparing GW572016 and letrozole versus letrozole in subjects with advanced or metastatic breast cancer [http://clinicaltrials.gov/ct/show/NCT00073528?order=2] (accessed 19 June 2007)
34. Clinicaltrials.gov. Fulvestrant with or without lapatinib in treating postmenopausal women with stage III or stage IV breast cancer that is hormone receptor-positive and expresses HER2 [http://clinicaltdals.gov/ show/NCT00390455] (accessed 30 April 2007)
35. Clinicaltrials.gov. Tykerb Evaluation After Chemotherapy (TEACH): lapatinib versus placebo in women with early-stage breast cancer [http://clinicaltrials.gov/ct/show/NCT00374322?order=1] (accessed 30 April 2007)
36. Clinicaltrials.gov. Adjuvant lapatinib and/or trastuzumab treatment optimisation study (ALTTO) [http://www.clinicaltrials.gov/ct/show/ NCT00490139?order=1] (accessed 26 September 2007)
37. Geyer CE et al: (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355: 2733-2743
38. De Bono J et al. (2003) Phase I and pharmacokinetic (PK) study of oral GW5720116, a potent reversible dual inhibitor of both ErbB1 and ErbB2 tyrosine kinase (TK), administered in combination with capecitabine [abstract #901]. J Clin Oncol 21 (Suppl)
39. Schwartz G et al. (2004) Phase I clinical, biology & pharmacakinetic study of the combination of GW572016 and capecitabine in patients with advanced solid tumors [abstract #3070]. J Clin Oncol 22 (Suppl)
40. Cameron D et al. (2007) Lapatinib (L) plus capecitabine (C) in HER2+ advanced breast cancer (ABC): Updated efficacy and biomarker analysis [abstract #1035]. J Clin Oncol 25 (Suppl)
41. Clayton AJ et al. (2004) Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91: 639-643
42. Yau T et al. (2006) Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab. Acta Oncol 45: 196-201
43. Lin NU et al. (2004) CNS metastases in breast cancer. J Clin Oncol 22: 3608-3617
44. Stemmler HJ et al. (2007) Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs 18: 23-28
45. Lin NU et al. (2006) Phase II trial of lapatinib for brain metastases in patients with HER2+ breast cancer [abstract #503]. J Clin Oncol 24 (Suppl)
46. Yang CH et al. (2005-2006) Systemic treatments for inflammatory breast cancer. Breast Dis 22: 55-65
47. Cristofanilli M et al. (2006) A phase II combination study of lapatinib and paclitaxel as a neoadjuvant therapy in patients with newly diagnosed inflammatory breast cancer (IBC) [abstract #1]. In Proceedings of the San Antonio Breast Cancer Symposium, 2006 December 14-17, San Antonio, TX
48. Trudeau M et al. (2006) Lapatinib (Tykerb) monotherapy in patients (pts) with recurrent inflammatory breast cancer (BC): Clinical activity and biologic predictors of response [abstract #1400]. Ann Oncol 17 (Suppi 9): Ix69
49. Clinicaltrials.gov. Docetaxel and lapatinib with or without combination chemotherapy or docetaxel and trastuzumab with combination chemotherapy in treating women with locally advanced, inflammatory, or resectable breast cancer [http://clinicaltrials.gov/ct/show/NCT00450892?order=1] (accessed 30 April 2007)
50. Storniolo A et al. (2005) A phase I, open-label study of lapatinib (GW572016) plus trastuzumab; a clinically active regimen [abstract #559]. J Clin Oncol 23: 18s
51. Chu I et al. (2005) The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. Cancer Res 65: 18-25
52. Clinicaltrials.gov. Lapatinib and tamoxifen in treating patients with locally advanced or metastatic breast cancer that did not respond to previous tamoxifen [http://clinicaltrials.gov/ct/show/ NCT00118157?order=2] (accessed 30 April 2007)
53. Chu Q et al. (2005) A phase I, open-label study of the safety, tolerability and pharmacokinetics of lapatinib (GW572016) in combination with letrozole in cancer patients [abstract #3001]. J Clin Oncol 23: 192s
54. Polychronis A et al. (2005) Preoperative gefitinib versus gefitinib and anastrozole in postmenopausal patients with oestrogen-receptor positive and epidermal-growth-factor-receptor-positive primary breast cancer: A double-blind placebo-controlled phase II randomised trial. Lancet Oncol 6: 383-391
55. Tuma RS (2007) Lapatinib moves forward in inflammatory and early HER2-positive breast cancer. J Natl Cancer Inst 99: 348-349