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NERLYNX
(NERATINIB)
Mariela Calo
Pharm. D. Candidate 2018
Howard University College of
Pharmacy
Community Rotation
Preceptor Angela Bryant
Overview
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Introduction
Indication
Mechanism of Action
Dosage and Administration
Warning and Precautions
Side Effects
Medication Counseling
Clinical Trial
Place in Therapy
Conclusion
Objectives
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To introduce the newly approved Nerlynx and its
indication
To explain the mechanism of action of this drug
To inform about the warnings and precautions for
patients taking Nerlynx
To list the side effects and medication counseling points
for this medication
To discuss the clinical study used for the approval of
Nerlynx
To understand the place in therapy of this new
medication
Nerlynx (neratinib)
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Antineoplastic
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Approved:
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Puma Biotechnology Inc.
Indication:
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July 17, 2017
Manufacturer:
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Kinase inhibitor
Early stage HER2+breast cancer
Available as:
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40 mg tablets
Indication
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Extended adjuvant treatment:
Adult patients
¤ With early stage
¤ HER2-overexpressed/amplified breast cancer
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After adjuvant trastuzumab-based therapy
Mechanism of Action
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Kinase inhibitor
Irreversibly inhibits:
EGFR
¤ HER2
¤ HER3
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Dosage and Administration
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240 mg daily (6 tablets)
With food
Continuously for 1 year
Anti-diarrheal prophylaxis:
Loperamide
¤ With the first dose and continue during first 2 cycles
(56 days)
¤ Instruct patients to maintain 1-2 bowel movements per
day and on how to use antidiarrheal treatment
regimens.
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Warnings and Precautions
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Diarrhea
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Hepatotoxicity
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Prophylaxis with loperamide recommended
Monitor liver function tests monthly for first 3 months,
then every 3 months of treatment
Embryo-fetal toxicity
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Can cause fetal harm
Side Effects
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Diarrhea
Nausea
Abdominal
pain
Fatigue
Vomiting
Rash
Stomatitis
Decreased
appetite
Muscle
spasms
AST/ALT
Increase
Nail
disorder
Dry skin
Weight
decrease
UTI
Pharmacokinetics
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Absorption
Food increases Cmax
¤ Tmax 2-8 hours
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Distribution
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Metabolism
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99% protein bound
Liver through CYP3A4
Excretion
97% Fecal excretion
¤ Half life à 7 to 17 hours
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Interactions
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Gastric acid reducing agents
PPI and H2-receptor antagonists
¤ Separate by 3 hours after antacid dosing
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Strong or moderate CYP3A4 inhibitors and inducers
P-glycoprotein substrates, specially with narrow
therapeutic index
Counseling
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Take daily with food at the same time each day.
If taking antacids, take Nerlynx 3 hours after taking
antacids.
Do not consume grapefruit products.
If missed dose, skip missed dose and continue normal
dosing schedule.
Female patients: avoid getting pregnant during
treatment and 1 month after end of treatment.
Male patients: Avoid pregnancy in partner during
treatment and for at least 3 months after end of
treatment.
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Clinical Trials
Clinical Trial For FDA Approval:
ExteNET trial (NCT00878709)
Clinical Trials
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Multicenter, randomized, double-blind, placebo-controlled study.
Study Design
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Methods
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2840 patients with early-stage HER2-positive breast cancer within two
years of completing treatment with adjuvant trastuzumab were
randomized to receive either NERLYNX (n=1420) or placebo (n=1420).
NERLYNX 240 mg or placebo was given orally once daily for one year.
Outcome measures
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Invasive disease- free survival (iDFS)
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Defined as the time between the date of randomization to the first occurrence
of invasive recurrence, distant recurrence, or death from any cause.
With 2 years and 28 days of follow-up.
Results
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Results
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Place in Therapy
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Cost:
$10,500 for a 30 day supply
¤ $126,000 for a year
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First extended adjuvant therapy for breast cancer
The indication was not restricted to hormonereceptor positive patients
No black box warning
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Even though 40% experience diarrhea
Ongoing Trials
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NALA Clinical Trial
Nerlynx with capecitabine versus lapatinib plus
capecitabine
¤ In patients HER2+ MBC patients who have received two
or more prior HER2 directed regimens in the metastatic
setting
¤ Estimated end date:
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February 2019
Conclusion
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Nerlynx is the first drug approved for adjuvant
therapy in breast cancer.
It is approved for patients that are HER2 positive
and have undergone trastuzumab therapy.
This drug has shown a statistically significant
reduction in cancer recurrence.
Can be an option that benefits a lot of patients.
References
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NERLYNX(TM) oral tablets, neratinib oral tablets. Puma Biotechnology, Inc (per FDA), Los Angeles, CA, 2017.
“Nerlynx Available for Extended Adjuvant Tx of HER2 Early Stage Breast Cancer.” MPR, 1 Aug. 2017,
www.empr.com/drug-news/nerlynx-available-for-extended-adjuvant-tx-of-her2-early-stage-breastcancer/article/678796/.
Weintraub, Arlene. “Puma to price new cancer med Nerlynx at a higher-than-Expected $10K per month: report.”
FiercePharma, 20 July 2017, www.fiercepharma.com/financials/puma-s-breast-cancer-drug-nerlynx-to-command-10k-amonth-despite-concerns-report.
Commissioner, Office of the. “Press Announcements - FDA approves new treatment to reduce the risk of breast cancer
returning.” U S Food and Drug Administration Home Page, Office of the Commissioner,
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm567309.htm.
Center for Drug Evaluation and Research. “Drug Approvals and Databases - Drug Trials Snapshot: NERLYNX.” U S Food and
Drug Administration Home Page, Center for Drug Evaluation and Research,
www.fda.gov/Drugs/InformationOnDrugs/ucm568138.htm.
Biotechnology, Puma. Puma Biotechnology, www.pumabiotechnology.com/pr20170717.html.
“Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast Cancer - Full
Text View.” Study Evaluating The Effects Of Neratinib After Adjuvant Trastuzumab In Women With Early Stage Breast
Cancer - Full Text View - ClinicalTrials.Gov, clinicaltrials.gov/ct2/show/study/NCT00878709#locn.
“A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2 Metastatic Breast Cancer
Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting - Full Text View.” A Study of
Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2 Metastatic Breast Cancer Who Have
Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting - Full Text View - ClinicalTrials.Gov,
clinicaltrials.gov/ct2/show/NCT01808573.
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Questions