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 HER2-positive 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.
Highlights
Two trials that investigated the addition of neratinib to standard therapy with paclitaxel, doxorubicin, and cyclophosphamide plus trastuzumab showed improved pathologic complete response (pCR) rates compared with the control groups, in the subset of patients with human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor-negative (HR–) breast cancer.[50,51]
Neratinib can improve outcomes when used as extended adjuvant therapy in select patients and in the treatment of patients with metastatic breast cancer (mBC), making this tyrosine kinase inhibitors (TKIs) an effective addition to the treatment paradigm for patients with HER2-positive breast cancer
A benefit with neratinib has been demonstrated in the metastatic setting after pertuzumab and T-DM1, there is currently no efficacy data available regarding the use of extended adjuvant neratinib following these therapies, as the ExteNET trial predates the use of pertuzumab and T-DM1 in early-stage breast cancer
Summary
The introduction of trastuzumab for the treatment of metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast. Patients with mBC receive pertuzumab in combination with trastuzumab and docetaxel as standard of care based on the significantly improved progression-free survival (PFS) and overall survival (OS) compared with trastuzumab and docetaxel observed in the CLEOPATRA trial.[1,2,23,24,25,26,27,28,29] The combination of trastuzumab and pertuzumab is active in the second-line setting in patients who have not yet received pertuzumab for metastatic disease, but T-DM1 is usually regarded as the second-line standard.[3,30,31] More recently, fam-trastuzumab deruxtecan-nxki demonstrated significant activity in patients in patients who had already received multiple anti-HER2–directed therapies, including T-DM1.32. 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 therapy and improve tolerability through management of neratinib-induced diarrhea
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