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Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials

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Abstract

Background

Neratinib is a novel pan-human epidermal growth factor receptor (HER) tyrosine kinase inhibitor that has shown promising activity against several types of malignancies, especially HER2-overexpressing breast cancer.

Objective

The objective of the current study was to provide a comprehensive insight into the efficacy and safety profiles of neratinib-based therapies.

Methods

Comprehensive literature searches of the PubMed, EMBASE, and Web of Science electronic databases were performed for all relevant clinical trials. Adverse events (AEs) of any grade and of grade 3 or higher were summarized and event rates were calculated. For controlled trials, odds ratios (ORs) were calculated to determine the role of neratinib in AEs. A random-effects model was applied if heterogeneity was observed (I2 ≥ 50%), otherwise a fixed-effects model was used. Kaplan–Meier survival curves were extracted for hazard ratio (HR) calculation, and survival outcomes were measured by progression-free survival (PFS) and overall survival (OS).

Results

Twenty-three studies and 4896 patients were included in the analysis. The most frequently occurring all-grade AEs in neratinib monotherapy were diarrhea (83.9%), nausea (37.9%), and abdominal pain (28.4%). The most common AEs for grades 3 or 4 were diarrhea (25.1%), dyspnea (5.6%), and abnormalities in liver enzyme levels (4.2%). Diarrhea, the most common AE, can be mitigated by prophylactic loperamide. Neratinib demonstrated promising clinical activity as monotherapy in HER2-positive breast cancer; however, in contrast, the effect became much less significant among HER2-mutated breast cancer patients. Notably, neratinib-based combination therapy achieved a higher response rate than neratinib monotherapy.

Conclusions

Neratinib-based therapies led to a higher frequency of some AEs, although these were mostly tolerable. Most studies demonstrated that neratinib provides a benefit in survival outcome. When combined with other anticancer agents, neratinib may hold promise for treating breast cancer with central nervous system metastases.

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Author notes

  1. Zhihang Tao and Xuelei Ma contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Number 37, Guoxue Alley, Chengdu, 610041, Sichuan, People’s Republic of China

    Zhihang Tao, Kai Shen, Yunuo Zhao, Hao Zeng & Xuelei Ma

  2. West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China

    Zhihang Tao, Kai Shen, Yunuo Zhao, Hao Zeng & Xuelei Ma

  3. Schulich School of Medicine and Dentistry, Western University, London, ON, Canada

    Stanley Xiangyu Li

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  1. Zhihang Tao
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Correspondence to Xuelei Ma.

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Zhihang Tao, Stanley Xiangyu Li, Kai Shen, Yunuo Zhao, Hao Zeng, and Xuelei Ma declare that they have no conflicts of interest.

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Tao, Z., Li, S.X., Shen, K. et al. Safety and Efficacy Profile of Neratinib: A Systematic Review and Meta-Analysis of 23 Prospective Clinical Trials. Clin Drug Investig 39, 27–43 (2019). https://doi.org/10.1007/s40261-018-0719-0

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