NCCN makes no warranties of any kind whatsoever regarding its content, use, or application and
disclaims any responsibility for how its content is applied or used, in any way.
NCCN: National Comprehensive Cancer Network.
IMPORTANT SAFETY INFORMATION
NERLYNX® (neratinib) tablets, for oral use
INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor
As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer,
to follow adjuvant trastuzumab-based therapy.
In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast
cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.
WARNINGS AND PRECAUTIONS:
Diarrhea: Aggressively manage diarrhea. If diarrhea occurs despite recommended prophylaxis, treat with additional
anti-diarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe
and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as
clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue
NERLYNX in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS: The most common adverse reactions (reported in ≥5% of patients) were:
NERLYNX as a single agent: diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite,
muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight
decreased, and urinary tract infection.
NERLYNX in combination with capecitabine: diarrhea, nausea, vomiting, decreased appetite, constipation,
fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract
infection, abdominal distention, renal impairment, and muscle spasms.
To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at
1-844-NERLYNX (1-844-637-5969) or FDA at 1-800-FDA-1088 or
Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. When patients require gastric acid
reducing agents, use an H2-receptor antagonist or antacid. Separate NERLYNX by at least 3 hours with antacids. Separate
NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists.
Strong CYP3A4 inhibitors: Avoid concomitant use.
Moderate CYP3A4 and P-glycoprotein (P-gp) dual inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates
when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:
Lactation: Advise women not to breastfeed.
For Full Prescribing Information, please
You are leaving this website
By clicking this link, you will be leaving the NERLYNX website and will be redirected to another webpage.
Gnant M, Martin M, Holmes FA, et al. Efficacy of neratinib in hormone receptor-positive patients who initiated treatment
within 1 year of completing trastuzumab-based adjuvant therapy in HER2+ early stage breast cancer: subgroup analyses
from the phase III ExteNET trial. Poster presented at: 2018 San Antonio Breast Cancer Symposium (SABCS); December 4-8,
2018; San Antonio, TX.
Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast
cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(12):1688-1700.
NERLYNX (neratinib) tablets Prescribing Information, Puma Biotechnology, Inc. 04/20.
Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in
HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet.
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.
Strasser-Weippl K, Horick N, Smith IE, et al. Long-term hazard of recurrence in HER2+ breast cancer patients untreated
with anti-HER2 therapy. Breast Cancer Res. 2015;17:56.
Recurrent breast cancer. Mayo Clinic website.
https://www.mayoclinic.org/diseases-conditions/recurrent-breast-cancer/symptoms-causes/syc-20377135. Accessed February
Sun L, Zhu Y, Qian Q, Tang L. Body mass index and prognosis of breast cancer: an analysis by menstruation status when
breast cancer diagnosis. Medicine (Baltimore). 2018;97(26):e11220.
Pierce JP, Patterson RE, Senger CM, et al. Lifetime cigarette smoking and breast cancer prognosis in the After Breast
Cancer Pooling Project. J Natl Cancer Inst. 2014;106(1):djt359.
Esserman LJ, Berry DA, DeMichele A, et al. Pathologic complete response predicts recurrence-free survival more
effectively by cancer subset: results from the I-SPY 1 trial—CALGB 150007/150012, ACRIN 6657. J Clin Oncol.
Helwick C. Final analysis of BCIRG-006 supports use of non–anthracycline-containing regimen in treatment of women with
early breast cancer. The ASCO Post website.
Accessed February 11, 2020.
Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med.
Von Minckwitz G, Huang C-S, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-628.
Singh JC, Jhaveri K, Esteva FJ. HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for
drug development. Br J Cancer. 2014;111(10):1888-1898.
Brufsky AM, Mayer M, Rugo HS, et al. Central nervous system metastases in patients with HER2-positive metastatic breast
cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011;17(14):4834-4843.
Untch M, Geyer CE Jr, Huang C-S, et al. Peripheral neuropathy (PN), thrombocytopenia (TCP) and central nervous system
(CNS) recurrence: an update of the phase III KATHERINE trial of post-neoadjuvant trastuzumab emtansine (T-DM1) or
trastuzumab (H) in patients (pts) with residual invasive HER2-positive breast cancer (BC). Slides presented at: 2019
European Society for Medical Oncology (ESMO) Annual Meeting; September 30, 2019; Barcelona, Spain.
Chien J. HER2+ early breast cancer: balancing risk and toxicity. Slides presented at: 2019 San Antonio Breast Cancer
Symposium (SABCS); December 11, 2019; San Antonio, TX.
Lin NU. Breast cancer brain metastases: new directions in systemic therapy. Ecancermedicalscience. 2013;7:307.
Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res. 2007;13(6):1648-1655.
Olson EM, Najita JS, Sohl J, et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive
metastatic breast cancer in the post-trastuzumab era. Breast. 2013;22(4):525-531.
Hegedüs C, Truta-Feles K, Antalffy G, et al. Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and
neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.
Biochem Pharmacol. 2012;84(3):260-267.
Puma Biotechnology, Inc. Data on file. 02/20.
Chan A, Hurvitz SA, Marx G, et al. Effect of prophylaxis or neratinib dose escalation on neratinib-associated diarrhea
and tolerability in patients with HER2-positive early-stage breast cancer: phase II CONTROL trial. Poster presented at:
2019 San Antonio Breast Cancer Symposium (SABCS); December 10-14, 2019; San Antonio, TX.
Puma Biotechnology. FDA ODAC Sponsor Presentation. May 24, 2017.
National Cancer Institute, National Institute of Health, US Department of Health and Human Services. Common Terminology
Criteria for Adverse Events (CTCAE) Version 4.0. Published May 28, 2009; Revised version 4.03 June 14, 2010.
Freedman RA, Gelman RS, Anders CK, et al. TBCRC 022: a phase II trial of neratinib and capecitabine for patients with
human epidermal growth factor receptor 2-positive breast cancer and brain metastases. J Clin Oncol.
Awada A, Colomer R, Inoue K, et al. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated
metastatic ERBB2-positive breast cancer: the NEfERT-T randomized clinical trial. JAMA Oncol. 2016;2(12):1557-1564.
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(11):3958-3965.
Wissner A, Mansour TS. The development of HKI-272 and related compounds for the treatment of cancer. Arch Pharm
Canonici A, Gijsen M, Mullooly M, et al. Neratinib overcomes trastuzumab resistance in HER2 amplified breast cancer.
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(1):47-58.
Collins DM, Conlon NT, Kannan S, et al. Preclinical characteristics of the irreversible pan-HER kinase inhibitor
neratinib compared with lapatinib: implications for the treatment of HER2-positive and HER2-mutated breast cancer.
Cancers (Basel). 2019;11(6):E737.
Prat A, Baselga J. The role of hormonal therapy in the management of hormonal-receptor-positive breast cancer with
co-expression of HER2. Nat Clin Pract Oncol. 2008;5(9):531-542.
Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clin Cancer Res. 2009;15(24):7479-7491.
Giuliano M, Trivedi MV, Schiff R. Bidirectional crosstalk between the estrogen receptor and human epidermal growth
factor receptor 2 signaling pathways in breast cancer: molecular basis and clinical implication. Breast
Chung A, Cui X, Audeh W, Giuliano A. Current status of anti-human epidermal growth factor receptor 2 therapies:
predicting and overcoming herceptin resistance. Clin Breast Cancer. 2013;13(4):223-232.
Paplomata E, Nahta R, O'Regan RM. Systemic therapy for early-stage HER2-positive breast cancers: time for a less-is-more
approach? Cancer. 2015;121(4):517-526.
Arpino G, Wiechmann L, Osborne CK, Schiff R. Crosstalk between the estrogen receptor and the HER tyrosine kinase
receptor family: molecular mechanism and clinical implications for endocrine therapy resistance. Endocr Rev.
Loi S, Dafni U, Karlis D, et al. Effects of estrogen receptor and human epidermal growth factor receptor-2 levels on the
efficacy of trastuzumab: a secondary analysis of the HERA trial. JAMA Oncol. 2016:2(8):1040-1047.
This information is intended for US healthcare professionals. Please
confirm you are a healthcare professional to continue.