Neratinib in HER2-Positive Breast Cancer Patients.

Neratinib in HER2-Positive Breast Cancer Patients.

Ann Pharmacother. 2019 Jan 04;:1060028018824088

Authors: Paranjpe R, Basatneh D, Tao G, De Angelis C, Noormohammed S, Ekinci E, Abughosh S, Ghose R, Trivedi MV

Abstract
OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib in human epidermal growth factor receptor (HER2)+ breast cancer (BC).
DATA SOURCES: A PubMed search was performed using the term neratinib between September 12, 2018, and November 21, 2018. References of published articles and reviews were also assessed for additional information.
STUDY SELECTION AND DATA EXTRACTION: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of neratinib were evaluated.
DATA SYNTHESIS: Neratinib, an irreversible inhibitor of HER1, HER2, and HER4, is Food and Drug Administration approved for the extended adjuvant treatment of stage I-III HER2+ BC to follow trastuzumab-based therapy. A phase III study has demonstrated statistically significant improvement in 5-year disease-free survival rate (90.2 vs 87.7; hazard ratio = 0.73, 95% CI = 0.57-0.92, P = 0.0083). Its most common adverse effect is diarrhea, observed in more than 90% of patients. The incidence of grade 3/4 diarrhea (~40%) is reduced by half with loperamide prophylaxis, which is recommended for the first 8 weeks of neratinib therapy. Other common adverse reactions are nausea and fatigue. The patients need to be monitored for liver function tests and drug interactions with acid-reducing agents, CYP3A4 inhibitors/inducers, and P-glycoprotein substrates with narrow therapeutic window. Relevance to Patient Care and Clinical Practice: American Society of Clinical Oncology and National Comprehensive Cancer Network clinical guidelines suggest the use of neratinib for extended adjuvant therapy following 1-year trastuzumab in stage I to III HER2+ BC. Diarrhea remains a clinically significant but manageable adverse event.
CONCLUSION: Neratinib significantly improves treatment outcomes and has manageable toxicity in stage I to III HER2+ BC patients.

PMID: 30607980 [PubMed - as supplied by publisher]

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