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Study Design Study Results Safety Dosing NCCN Guidelines®

EARLY-STAGE STUDY RESULTS
Early-Stage Study Results

NERLYNX prevents recurrence1,*

INVASIVE DISEASE-FREE SURVIVAL (iDFS) IN HER2+, HR+ POPULATION: PATIENTS COMPLETING PRIOR TRASTUZUMAB-BASED THERAPY ≤1 YEAR FROM RANDOMIZATION1

iDFS chart

42% reduction in risk of recurrence*,†

95% of the patients with HER2+, HR+ disease had concomitant endocrine therapy.2

iDFS in the ITT population (N=2840): 94.2% with NERLYNX (95% CI: 92.6%, 95.4%) vs 91.9% with placebo (95% CI: 90.2%, 93.2%) at 2 years (HR=0.66; 95% CI: 0.49, 0.90; P=0.008)3
  • 72% of patients in the ExteNET ITT population had stage II or III disease (41% stage II, 31% stage III). Staging was unknown for 18% of patients3

CI: confidence interval; HER: human epidermal growth factor receptor; HR: hazard ratio; HR+: hormone receptor-positive; ITT: intent-to-treat.

*Recurrence was defined as time from randomization to first occurrence of invasive ipsilateral tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence, or death from any cause.1

†Results of ExteNET are supported by an exploratory analysis of 5-year follow-up, with 74.5% (2117/2840) of patients reconsented.2

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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.

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NERLYNX prevents distant recurrence1,*

DISTANT DISEASE–FREE SURVIVAL (DDFS) IN HER2+, HR+ population: patients completing prior trastuzumab-BASED THERAPY ≤1 year from randomization1

DDFS chart

43% reduction in risk of distant recurrence*,†

95% of the patients with HER2+, HR+ disease had concomitant endocrine therapy.2

CI: confidence interval; HER: human epidermal growth factor receptor; HR: hazard ratio; HR+: hormone receptor-positive;

*Distant recurrence is defined as the first occurrence of distant recurrence or death from any cause.2

†Results of ExteNET are supported by an exploratory analysis of 5-year follow-up, with 74.5% (2117/2840) of patients reconsented.2

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Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.

Lactation: Advise women not to breastfeed.

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NERLYNX prevents recurrence in patients who did not achieve a PCR1,*

INVASIVE DISEASE–FREE SURVIVAL (iDFS) IN HER2+, HR+ POPULATION WHO DID NOT ACHIEVE A PCR AFTER NEOADJUVANT THERAPY: PATIENTS COMPLETING PRIOR TRASTUZUMAB-BASED THERAPY ≤1 YEAR FROM RANDOMIZATION†

iDFS chart

40% reduction in risk of recurrence*

95% of the patients with HER2+, HR+ disease had concomitant endocrine therapy.2

CI: confidence interval; HER: human epidermal growth factor receptor; HR: hazard ratio; HR+: hormone receptor-positive; pCR: pathologic complete response.

*Recurrence is defined as an invasive-disease event or death.1

†Results of ExteNET are supported by an exploratory analysis of 5-year follow-up, with 74.5% (2117/2840) of patients reconsented.2

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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.

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NERLYNX prevents recurrence across prespecified subgroups

ITT POPULATION: INVASIVE DISEASE-FREE SURVIVAL (iDFS) BENEFIT AT 2 YEARS, BY SUBGROUP

3 3 22 3 22 3

CI: confidence interval; HR: hazard ratio; ITT: intent-to-treat.

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Drug interactions: 1. 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. 2. Strong CYP3A4 inhibitors: Avoid concomitant use. 3. Moderate CYP3A4 and P-glycoprotein (P-gp) dual inhibitors: Avoid concomitant use. 4. Strong or moderate CYP3A4 inducers: Avoid concomitant use. 5. P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.

Please see additional IMPORTANT SAFETY INFORMATION below.

Learn about adverse events

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 (neratinib) tablets Prescribing Information, Puma Biotechnology, Inc. 04/20.
  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.
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  14. 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.
  15. 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.
  16. 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.
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  22. Puma Biotechnology, Inc. Data on file. 02/20.
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  24. Puma Biotechnology. FDA ODAC Sponsor Presentation. May 24, 2017.
  25. 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.
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