Clinical Drug Investigation

, Volume 39, Issue 1, pp 27–43 | Cite as

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

  • Zhihang Tao
  • Stanley Xiangyu Li
  • Kai Shen
  • Yunuo Zhao
  • Hao Zeng
  • Xuelei MaEmail author
Systematic Review



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.


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


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).


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.


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.


Compliance with Ethical Standards


There was no funding associated with the completion of this work.

Conflict of interest

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

Supplementary material

40261_2018_719_MOESM1_ESM.pdf (8 mb)
Supplementary material 1 (PDF 8230 kb)


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China HospitalSichuan UniversityChengduPeople’s Republic of China
  2. 2.West China School of Medicine, West China HospitalSichuan UniversityChengduPeople’s Republic of China
  3. 3.Schulich School of Medicine and DentistryWestern UniversityLondonCanada

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