Optimal Strategies for Successful Initiation of Neratinib in Patients with HER2-Positive Breast Cancer

Abstract

Neratinib is an irreversible, pan-human epidermal growth factor inhibitor that has shown efficacy across human epidermal growth factor receptor 2 (HER2)-positive breast cancer settings. Neratinib is indicated for use as extended adjuvant therapy for HER2-positive early-stage breast cancer or, in combination with capecitabine, in the treatment of HER2positive metastatic breast cancer. The primary tolerability concern with neratinib is diarrhea, and severe diarrhea early in treatment can lead to a substantial proportion of patients discontinuing neratinib, which may lead to reduced or nonexistent efficacy. In order to establish a set of treatment recommendations for use of neratinib, on May 12, 2020, an expert panel of oncologists and gastroenterologists met virtually to discuss the role of neratinib in the treatment of patients with HER2-positive breast cancer. The panel reviewed the current data on neratinib, including efficacy across settings and diarrhea management strategies. Based on these data and their clinical experience, the panelists developed a set of recommendations to guide selection of patients for neratinib, implement weekly dose escalation at initiation of therapy, and prophylactically manage diarrhea.

Globally Approved EGFR Inhibitors: Insights into Their Syntheses, Target Kinases, Biological Activities, Receptor Interactions, and Metabolism

“…Neratinib Approval History Neratinib (Figure 43) is an irreversible inhibitor of the EGFR, HER2/4 receptor tyrosine kinase, which was approved on 17 July 2017 for use in the treatment of HER2-positive breast cancer [114]. In 2020, it was also approved for HER2-positive metastatic breast cancer [115].…”

Management of Diarrhea in Patients with HER2-Positive Breast Cancer Treated with Neratinib: A Case Series and Summary of the Literature

“…The 2-week DE schedule (week 1 = 120 mg/day, week 2 = 160 mg/day, week 3 and onwards: 240 mg/day) has been included in the FDA label for both HER2+ ESBC and MBC since June 2021 [ 31 ]. An alternative DE schedule with a panel recommendation to start neratinib at a dose of 120 mg/day with PRN loperamide and escalate the dose by 40 mg/day each week until patients reach the recommended dose of 240 mg/day of neratinib has also been published [ 45 ].…”

“…ESBC and MBC since June 2021 [31]. An alternative DE schedule with a panel recommendation to start neratinib at a dose of 120 mg/day with PRN loperamide and escalate the dose by 40 mg/day each week until patients reach the recommended dose of 240 mg/day of neratinib has also been published [45].…”

Development and Characterization of Oral Raft Forming In Situ Gelling System of Neratinib Anticancer Drug Using 32 Factorial Design

“…Approximately 90-95% of breast cancer cases are due to sedentary lifestyle and environmental factors, and around 5-10% of breast cancer cases are due to genetic disorders [5,6]. The core origin of this cancer is the lining of epithelial cells in the terminal duct of the lobule [7].…”