Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations

References

• Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–182.
   PubMed Web of Science ®Google Scholar
• Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28:3271–3277.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Angulo AM, Litton JK, Broglio KR, et al. High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller. J Clin Oncol. 2009;27:5700–5706.
   PubMed Web of Science ®Google Scholar
• Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–1283.
   PubMed Web of Science ®Google Scholar
• Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382:1021–1028.
   PubMed Web of Science ®Google Scholar
• Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783–792.
   PubMed Web of Science ®Google Scholar
• Swain SM, Baselga J, Kim SB, et al. CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372:724–734.
   PubMed Web of Science ®Google Scholar
• Garrett JT, Arteaga CL. Resistance to HER2-directed antibodies and tyrosine kinase inhibitors: mechanisms and clinical implications. Cancer Biol Ther. 2011;11:793–800.
   PubMed Web of Science ®Google Scholar
• Wilken JA, Maihle NJ. Primary trastuzumab resistance: new tricks for an old drug. Ann N Y Acad Sci. 2010;1210:53–65.
   PubMed Web of Science ®Google Scholar
• Nahta R, Yu D, Hung M-C, et al. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006;3:269–280.
   PubMedGoogle Scholar
• Pestalozzi BC, Holmes E, de Azambuja E, et al. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol. 2013;14:244–248.
   PubMed Web of Science ®Google Scholar
• Rabindran SK, Discafani CM, Rosfjord EC, et al. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004;64:3958–3965.
   PubMed Web of Science ®Google Scholar
• Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9:463–475.
   PubMed Web of Science ®Google Scholar
• Linggi B, Carpenter G. ErbB receptors: new insights on mechanisms and biology. Trends Cell Biol. 2006;16:649–656.
   PubMed Web of Science ®Google Scholar
• Zhang X, Gureasko J, Shen K, et al. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell. 2006;125:1137–1149.
   PubMed Web of Science ®Google Scholar
• Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.
   PubMed Web of Science ®Google Scholar
• Dankort D, Maslikowski B, Warner N, et al. Grb2 and Shc adapter proteins play distinct roles in Neu (ErbB-2)-induced mammary tumorigenesis: implications for human breast cancer. Mol Cell Biol. 2001;21:1540–1551.
   PubMed Web of Science ®Google Scholar
• Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26:6469–6487.
   PubMed Web of Science ®Google Scholar
• Klapper LN, Glathe S, Vaisman N, et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci USA. 1999;96:4995–5000.
   PubMed Web of Science ®Google Scholar
• Cho HS, Mason K, Ramyar KX, et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature. 2003;421:756–760.
   PubMed Web of Science ®Google Scholar
• Graus-Porta D, Beerli RR, Daly JM, et al. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. Embo J. 1997;16:1647–1655.
   PubMed Web of Science ®Google Scholar
• Nahta R, Esteva FJ. Herceptin: mechanisms of action and resistance. Cancer Lett. 2006;232:123–138.
   PubMed Web of Science ®Google Scholar
• Way TD, Lin JK. Role of HER2/HER3 co-receptor in breast carcinogenesis. Future Oncol. 2005;1:841–849.
   PubMedGoogle Scholar
• Lee JW, Soung YH, Seo SH, et al. Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas. Clin Cancer Res. 2006;12:57–61.
   PubMed Web of Science ®Google Scholar
• Bose R, Kavuri SM, Searleman AC, et al. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov. 2013;3:224–237.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.
   PubMed Web of Science ®Google Scholar
• Boulbes DR, Arold ST, Chauhan GB, et al. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer. Mol Oncol. 2015;9:586–600.
   PubMed Web of Science ®Google Scholar
• Adams CW, Allison DE, Flagella K, et al. Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab. Cancer Immunol Immunother. 2006;55:717–727.
   PubMed Web of Science ®Google Scholar
• National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer version 1, 2016. [cited 2016 Feb 22] Available from: http://www.nccn.org/
   Google Scholar
• Cardoso F, Costa A, Norton L, et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Ann Oncol. 2014;25:1871–1888.
   PubMed Web of Science ®Google Scholar
• Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–119.
   PubMed Web of Science ®Google Scholar
• Swain SM, Kim SB, Cortés J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461–471.
   PubMed Web of Science ®Google Scholar
• Verma S, Miles D, Gianni L, et al. EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783–1791.
   PubMed Web of Science ®Google Scholar
• Ellis PA, Barrios CH, Eiermann W, et al. Phase III, randomized study of trastuzumab emtansine (T-DM1) ± pertuzumab (P) vs trastuzumab + taxane (HT) for first-line treatment of HER2-positive MBC: primary results from the MARIANNE study. J Clin Oncol. 2015;33(suppl), abstract 507.
   Google Scholar
• Krop IE, Kim SB, González-Martín A, et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:689–699.
   PubMed Web of Science ®Google Scholar
• Wildiers H, Kim S-B, Gonzalez-Martin A, et al. Trastuzumab emtansine improves overall survival versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer: Final overall survival results from the phase 3 TH3RESA study. 38th Annual San Antonio Breast Cancer Symposium; 8–12 Dec; San Antonio, TX; 2015. Abstract S5-05
   Google Scholar
• Burstein HJ, Keshaviah A, Baron AD, et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: the trastuzumab and vinorelbine or taxane study. Cancer. 2007;110:965–972.
   PubMed Web of Science ®Google Scholar
• Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006;24:2786–2792.
   PubMed Web of Science ®Google Scholar
• von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/Breast International Group 03-05 study. J Clin Oncol. 2009;27:1999–2006.
   PubMed Web of Science ®Google Scholar
• Blackwell KL, Burstein HJ, Storniolo AM, et al. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28:1124–1130.
   PubMed Web of Science ®Google Scholar
• Blackwell KL, Burstein HJ, Storniolo AM, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study. J Clin Oncol. 2012;30:2585–2592.
   PubMed Web of Science ®Google Scholar
• Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–2743.
   PubMed Web of Science ®Google Scholar
• Cameron D, Casey M, Oliva C, et al. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15:924–934.
   PubMed Web of Science ®Google Scholar
• Senkus E, Kyriakides S, Ohno S, et al. Primary breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v8–v30.
   PubMed Web of Science ®Google Scholar
• Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12:236–244.
   PubMed Web of Science ®Google Scholar
• Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014;32:3744–3752.
   PubMed Web of Science ®Google Scholar
• Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.
   PubMed Web of Science ®Google Scholar
• Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17:367–377.
   PubMed Web of Science ®Google Scholar
• Tsou HR, Overbeek-Klumpers EG, Hallett WA, et al. Optimization of 6,7-disubstituted-4-(arylamino)quinoline-3-carbonitriles as orally active, irreversible inhibitors of human epidermal growth factor receptor-2 kinase activity. J Med Chem. 2005;48:1107–1131.
   PubMed Web of Science ®Google Scholar
• Wissner A, Mansour TS. The development of HKI-272 and related compounds for the treatment of cancer. Arch Pharm (Weinheim). 2008;341:465–477.
   PubMed Web of Science ®Google Scholar
• Davis MI, Hunt JP, Herrgard S, et al. Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011;29:1046–1051.
   PubMed Web of Science ®Google Scholar
• Rabindran SK. Antitumor activity of HER-2 inhibitors. Cancer Lett. 2005;227:9–23.
   PubMed Web of Science ®Google Scholar
• Canonici A, Gijsen M, Mullooly M, et al. Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer. Oncotarget. 2013;4:1592–1605.
   PubMed Web of Science ®Google Scholar
• O’Brien NA, Browne BC, Chow L, et al. Activated phosphoinositide 3-kinase/AKT signaling confers resistance to trastuzumab but not lapatinib. Mol Cancer Ther. 2010;9:1489–1502.
   PubMed Web of Science ®Google Scholar
• Mohd Nafi SN, Generali D, Kramer-Marek G, et al. Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer. Oncotarget. 2014;5:5934–5949.
   PubMed Web of Science ®Google Scholar
• Xia W, Petricoin EF 3rd, Zhao S, et al. An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models. Breast Cancer Res. 2013;15:R85.
   PubMed Web of Science ®Google Scholar
• Zhao XQ, Xie JD, Chen XG, et al. Neratinib reverses ATP-binding cassette B1-mediated chemotherapeutic drug resistance in vitro, in vivo, and ex vivo. Mol Pharmacol. 2012;82:47–58.
   PubMed Web of Science ®Google Scholar
• Abbas R, Hug BA, Leister C, et al. A double-blind, randomized, multiple-dose, parallel-group study to characterize the occurrence of diarrhea following two different dosing regimens of neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor. Cancer Chemother Pharmacol. 2012;70:191–199.
   PubMed Web of Science ®Google Scholar
• Hug B, Abbas R, Leister C, et al. A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects. Clin Cancer Res. 2010;16:4016–4023.
   PubMed Web of Science ®Google Scholar
• Wong KK, Fracasso PM, Bukowski RM, et al. A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin Cancer Res. 2009;1:2552–2558.
   Web of Science ®Google Scholar
• Burstein HJ, Sun Y, Dirix LY, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. J Clin Oncol. 2010;28:1301–1307.
   PubMed Web of Science ®Google Scholar
• Abbas R, Hug BA, Leister C, et al. Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects. Br J Clin Pharmacol. 2011;71:522–527.
   PubMed Web of Science ®Google Scholar
• Wang J, Li-Chan XX, Atherton J, et al. Characterization of HKI-272 covalent binding to human serum albumin. Drug Metab Dispos. 2010;38:1083–1093.
   PubMed Web of Science ®Google Scholar
• Ito Y, Suenaga M, Hatake K, et al. Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study. Jpn J Clin Oncol. 2012;42:278–286.
   PubMed Web of Science ®Google Scholar
• Awada A, Dirix L, Manso Sanchez L, et al. Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. Ann Oncol. 2013;24:109–116.
   PubMed Web of Science ®Google Scholar
• Chow LW, Xu B, Gupta S, et al. Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. Br J Cancer. 2013;108:1985–1993.
   PubMed Web of Science ®Google Scholar
• Gandhi L, Bahleda R, Tolaney SM, et al. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J Clin Oncol. 2014;32:68–75.
   PubMed Web of Science ®Google Scholar
• Martin M, Bonneterre J, Geyer CE, et al. A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer. Eur J Cancer. 2013;49:3763–3772.
   PubMed Web of Science ®Google Scholar
• Awada A, Colomer R, Inoue K, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic HER2-positive breast cancer: the NEfERT-T randomized clinical trial. JAMA Oncol. 2016; doi:10.1001/jamaoncol.2016.0237. [Epub ahead of print]
   PubMedGoogle Scholar
• Saura C, Garcia-Saenz JA, Xu B, et al. Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2014;32:3626–3633.
   PubMed Web of Science ®Google Scholar
• Swaby R, Blackwell K, Jiang Z, et al. Neratinib in combination with trastuzumab for the treatment of advanced breast cancer: A phase I/II study. J Clin Oncol. 2009. Abstract 1004.
   Web of Science ®Google Scholar
• Jankowitz RC, Abraham J, Tan AR, et al. Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2-positive breast cancer: an NSABP Foundation Research Program phase I study. Cancer Chemother Pharmacol. 2013;72:1205–1212.
   PubMed Web of Science ®Google Scholar
• Gajria D, Modi S, Saura C, et al. A phase I/II study of neratinib plus temsirolimus in HER2+ metastatic breast cancer reveals ongoing HER2 pathway dependence in many patients despite several lines of HER2 targeted therapy. Cancer Res. 2015;75: P5-19-04. [cited 2016 Feb 21]. Available from: http://cancerres.aacrjournals.org/content/75/9_Supplement/P5-19-04.short?rss=1
   Web of Science ®Google Scholar
• Freedman RA, Gelman RS, Wefel JS, et al. Translational Breast Cancer Research Consortium (TBCRC) 022: a phase II trial of neratinib for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol. 2016;20;34(9):945–952.
   Web of Science ®Google Scholar
• Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in early-stage HER2+ breast cancer: 3-year analysis from a phase 3 randomized, placebo-controlled double-blind trial (ExteNET). 38th Annual San Antonio Breast Cancer Symposium; 8–12 Dec; San Antonio, TX; 2015. Oral presentation.
   Google Scholar
• Park JW, Liu MC, Yee D, et al. Neratinib plus standard neoadjuvant therapy for high-risk breast cancer: efficacy results from the I-SPY 2 trial. 105th Annual Meeting of the American Association for Cancer Research 5-9 April 5-9 2014, abstract CT227. [cited 2016 Feb 23] Available from: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3404&sKey=ed5341ec-ef13-493e-8844-e14be322679c&cKey=d9b44ad7-1673-4ec9-b360-11254fbb92be&mKey=6ffe1446-a164-476a-92e7-c26446874d93
   Google Scholar
• Jacobs SA, Robidoux A, Garcia JMP, et al. NSABP FB-7: A phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide (AC) with postoperative T in women with locally advanced HER2-positive breast cancer. 38th Annual San Antonio Breast Cancer Symposium; 8–12 Dec; San Antonio, TX; 2015. Poster PD5-04.
   Google Scholar
• Hyman DM, Piha-Paul SA, Rodón J, et al. Neratinib for ERBB2 mutant, HER2 non-amplified, metastatic breast cancer: Preliminary analysis from a multicenter, open-label, multi-histology phase II basket trial. 38th Annual San Antonio Breast Cancer Symposium; 8–12 Dec; San Antonio, TX; 2015. Poster PD5-05.
   Google Scholar
• Ustaris F, Saura C, Di Palma J, et al. Effective management and prevention of neratinib-induced diarrhea. Am J Hematol/Oncol. 2015;11:13–22.
   Google Scholar
• Besse B, Soria J, Yao B, et al. Neratinib with or without temsirolimus in patients with non-small cell lung cancer (NSCLC) carrying HER2 somatic mutations: an international randomized phase II study. Ann Oncol. 2014;25:1–41. abstract A39
   Google Scholar
• Harbeck N, Huang CS, Hurvitz S, et al. Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol. 2016;17:357–366.
   PubMed Web of Science ®Google Scholar
• Cortés J, Dieras V, Ro J, et al. Afatinib alone or afatinib plus vinorelbine versus investigator’s choice of treatment for HER2-positive breast cancer with progressive brain metastases after trastuzumab, lapatinib, or both (LUX-Breast 3): a randomised, open-label, multicentre, phase 2 trial. Lancet Oncol. 2015;16:1700–1710.
   PubMed Web of Science ®Google Scholar
• Bachelot T, Romieu G, Campone M, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study. Lancet Oncol. 2013;14:64–71.
   PubMed Web of Science ®Google Scholar
• Lin NU, Diéras V, Paul D, et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009;15:1452–1459.
   PubMed Web of Science ®Google Scholar