Efficacy

HR+ POPULATION: PATIENTS COMPLETING PRIOR TRASTUZUMAB ≤ 1 YEAR FROM RANDOMIZATION

NERLYNX significantly improved invasive disease-free survival (iDFS) versus placebo at 5 years2

HR+ 5-year analysis: Patients completing prior trastuzumab ≤ 1 year from randomization

42% reduction in risk of recurrence

95% of the HR+ study population received concurrent endocrine therapy.

CI: confidence interval; HER2: human epidermal growth factor receptor 2; HR: hazard ratio; HR+: hormone receptor-positive

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

Unstratified.

Recurrence is defined as an invasive disease event or death.

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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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HR+ POPULATION: PATIENTS COMPLETING PRIOR TRASTUZUMAB ≤ 1 YEAR FROM RANDOMIZATION

NERLYNX demonstrated a 42% reduction in risk of distant recurrence* at 5 years2

NERLYNX maintained benefit across all endpoints at 5 years

95% of the HR+ study population received concurrent endocrine therapy.

CI: confidence interval; HER2: human epidermal growth factor receptor 2; HR: hazard ratio; HR+: hormone receptor-positive

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

Unstratified.

Stratified.

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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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INTENT-TO-TREAT POPULATION

NERLYNX significantly improved iDFS versus placebo after adjuvant therapy1

ITT patient population: iDFS at 2 years

iDFS in patients with centrally confirmed tumor tissue samples at 2 years = 94.6% in the NERLYNX arm, 91.4% in the placebo arm, representing a 43% reduction in the risk of recurrence for patients taking NERLYNX (3.2% absolute benefit), HR = 0.57 (95% CI: 0.39, 0.84).2,†

CI: confidence interval; HER2: human epidermal growth factor receptor 2; HR: hazard ratio; iDFS: invasive disease-free survival; ITT: intent to treat

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

Central confirmation was not a stratification factor. In the prespecified analysis, 76.1% of patients enrolled had tumor tissue ascertained by central testing for HER2 gene amplification.

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The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.

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INTENT-TO-TREAT POPULATION

At the 5-year exploratory analysis, NERLYNX iDFS results were consistent with the 2-year data5

ITT patient population: iDFS at 5 years

The iDFS results of ExteNET are supported by an exploratory analysis of 5-year follow-up with 74.5% (2117/2840) of patients reconsented.

CI: confidence interval; HR: hazard ratio; iDFS: invasive disease-free survival; ITT: intent to treat

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

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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 or moderate CYP3A4 inhibitors: Avoid concomitant use. 3. Strong or moderate CYP3A4 inducers: Avoid concomitant use. 4. 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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SUBGROUP ANALYSIS

NERLYNX provided an iDFS benefit across several prespecified subgroups at 2 years20

PUMACO4204_HCP-Site_2.1_charts

CI: confidence interval; HR: hazard ratio; iDFS: invasive disease-free survival

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Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, 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.

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Learn about adverse events

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS: The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com 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.