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Study Design Study Results Safety Dosing NCCN Guidelines®

EARLY-STAGE STUDY RESULTS
Early-Stage Study Results

NERLYNX prevents recurrence1,*

DESCRIPTIVE ANALYSES: INVASIVE DISEASE-FREE SURVIVAL (iDFS) AT 5 YEARS IN HER2+, HR+ POPULATION PATIENTS COMPLETING PRIOR TRASTUZUMAB-BASED THERAPY ≤1 YEAR FROM RANDOMIZATION (n=1334)

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

*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.

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

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

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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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Invasive disease-free survival (iDFS) benefit across several prespecified subgroups

ITT POPULATION: iDFS BENEFIT AT 2 YEARS, BY SUBGROUP21

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

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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,*

DESCRIPTIVE ANALYSES: INVASIVE DISEASE-FREE SURVIVAL (iDFS) AT 5 YEARS IN HER2+ HR+ PATIENTS WHO COMPLETED PRIOR TRASTUZUMAB-BASED THERAPY ≤1 YEAR FROM RANDOMIZATION AND DID NOT ACHIEVE A pCR (n=295)†

DDFS chart

40% reduction in risk of recurrence*,†

  • ExteNET was a pivotal phase 3, global, multicenter, randomized, double-blind, placebo-controlled study of NERLYNX 240 mg/day for 1 year (n=1420) vs placebo (n=1420) in patients with early-stage HER2+ breast cancer (N=2840). The primary endpoint in ExteNET was iDFS.2,3
  • 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

*Recurrence is defined as the 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.

†Results of ExteNET are supported by descriptive analyses after 5 years of follow-up, with 74.5% of patients (2117/2840) reconsented. 95% of the patients with HER2+ HR+ disease had concomitant endocrine therapy. Data in HER2+ HR+ patients who did not achieve a pCR were derived from a descriptive subgroup analysis.2

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

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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.

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NERLYNX increases overall survival (OS) in patients who did not achieve a pCR1

DESCRIPTIVE ANALYSES: OS AT 8 YEARS IN HER2+ HR+ PATIENTS WHO COMPLETED PRIOR TRASTUZUMAB-BASED THERAPY ≤1 YEAR FROM RANDOMIZATION AND DID NOT ACHIEVE A pCR (n=295)*

iDFS chart

53% reduction in risk of death*

  • 2.1% absolute benefit in OS at 8 years vs placebo in HER2+ HR+ patients who completed prior trastuzumab-based therapy ≤1 year from randomization (n=1334) (HR=0.79; 95% CI: 0.55-1.13)
  • After a median follow-up of 8 years there was no statistically significant difference in OS between NERLYNX and placebo (HR=0.95; 95% CI: 0.75-1.21). The 5-year estimate of OS was 94.1% (95% CI: 92.7%-95.3%) with NERLYNX and 93.3% (95% CI: 91.8%-94.5%) with placebo3

*95% of the patients with HER2+ HR+ disease had concomitant endocrine therapy. Data in HER2+ HR+ patients who did not achieve a pCR were derived from a descriptive subgroup analysis.1,2

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

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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.

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NERLYNX prevents CNS metastases in patients who did not achieve a pCR1

DESCRIPTIVE ANALYSES: HER2+ HR+ PATIENTS COMPLETING PRIOR TRASTUZUMAB-BASED THERAPY ≤1 YEAR FROM RANDOMIZATION WHO DID NOT ACHIEVE A pCR (n=295)*

0.8% (95% CI: 0.1%-4.0%) of patients (n=131) experienced CNS recurrence as the first site of metastases with NERLYNX vs 3.6% (95% CI: 1.3%-7.8%) of patients (n=164) with placebo.

76% reduction in the risk of CNS recurrence or death from any cause 98.4% (95% CI: 93.6%-99.6%) of patients (n=131) experienced CNS-DFS at 5 years with NERLYNX vs 92.0% (95% CI: 85.6%-95.7%) of patients (n=164) with placebo (HR=0.24; 95% CI: 0.04-0.92).

*Results of ExteNET are supported by descriptive analyses after 5 years of follow-up, with 74.5% of patients (2117/2840) reconsented. Data in HER2+ HR+ patients who did not achieve a pCR were derived from a descriptive subgroup analysis.1,2

CI: confidence interval; CNS: central nervous system; CNS-DFS: central nervous system disease-free survival; HER: human epidermal growth factor receptor; HR: hazard ratio; HR+: hormone receptor–positive; pCR: pathologic complete response.

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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.

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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  3. NERLYNX [package insert]. Los Angeles, CA: Puma Biotechnology, Inc.
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  21. Puma Biotechnology, Inc. Data on file
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