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Study Design Study Results Safety Dosing NCCN Guidelines®

In HER2+ metastatic disease:

Neratinib (NERLYNX) is included as part of 2 treatment options for recurrent HER2+ breast cancer CNS metastases in the NCCN Guidelines® for Central Nervous System Cancers27
Original guideline inclusion: March 20, 2018

Category 2A*:
Neratinib + Capecitabine27

TBCRC 022 A Phase 2 Trial of Neratinib and Capecitabine for Patients With HER2+ Breast Cancer and Brain Metastases (NCT01494662)28

TBCRC 022: Neratinib + capecitabine active against progressive brain metastases in patients with HER2+ brain metastases28

NALA A Phase 3 Trial of Neratinib + Capecitabine vs Lapatinib + Capecitabine for Patients With HER2+ Breast Cancer After ≥2 HER2-Directed Regimens in the Metastatic Setting (NCT01808573)26

NALA: Neratinib + capecitabine active against symptomatic brain metastases in patients with HER2+ breast cancer26

Category 2B*:
Neratinib + Paclitaxel27

NEfERT-T Randomized, Multicenter, International Study of HER2-Directed Therapy in First-Line mBC (NCT00915018)29

NEfERT-T: Reduced CNS progression with neratinib + paclitaxel in patients with HER2+ brain metastases29

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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.

*Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.27

CNS: central nervous system; HER: human epidermal growth factor receptor; mBC: metastatic breast cancer; NCCN: National Comprehensive Cancer Network.

Select IMPORTANT SAFETY INFORMATION

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.

Please see additional IMPORTANT SAFETY INFORMATION below.

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated:

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS: The most common adverse reactions (reported in ≥5% of patients) were:

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 www.fda.gov/medwatch.

DRUG INTERACTIONS:

USE IN SPECIFIC POPULATIONS:

For Full Prescribing Information, please click here.

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Reference:

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  2. 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.
  3. NERLYNX [package insert]. Los Angeles, CA: Puma Biotechnology, Inc.
  4. 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. 2017;389(10075):1195-1205.
  5. 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(33):3744-3752.
  6. Yee D. Pathological complete response predicts event-free and distant disease free survival in the I-SPY 2 TRIAL. Slides presented at: 2017 San Antonio Breast Cancer Symposium (SABCS); December 5-9, 2017; San Antonio, TX.
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  15. 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) Congress; September 30, 2019; Barcelona, Spain.
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  18. Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res. 2007;13(6):1648-1655.
  19. 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.
  20. 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.
  21. Puma Biotechnology, Inc. Data on file
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  23. Puma Biotechnology. FDA ODAC Sponsor Presentation. May 24, 2017.
  24. US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf. Accessed August 7, 2020.
  25. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.5.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed July 24, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org.
  26. Saura C, Oliveira M, Feng Y-H, et al. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with ≥2 HER2- directed regimens: phase III NALA trial. J Clin Oncol. Published online July 17, 2020. doi:10.1200/JCO.20.00147
  27. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.2.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed July 24, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org.
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