Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer

Hiroji Iwata; Norikazu Masuda; Sung-Bae Kim; Kenichi Inoue; Yoshiaki Rai; Takashi Fujita; Joanne Chiu; Shoichiro Ohtani; Masato Takahashi; Toshiko Miyaki; Yen-Shen Lu; Binghe Xu; Yoon Sim Yap; Anita Bustam; Bin Yao; Bo Zhang; Richard Bryce; Arlene Chan

doi:10.2217/fon-2019-0143

Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer

Future Oncol. 2019 Jul;15(21):2489-2501. doi: 10.2217/fon-2019-0143. Epub 2019 May 29.

Authors

Hiroji Iwata¹, Norikazu Masuda², Sung-Bae Kim³, Kenichi Inoue⁴, Yoshiaki Rai⁵, Takashi Fujita⁶, Joanne Chiu⁷, Shoichiro Ohtani⁸, Masato Takahashi⁹, Toshiko Miyaki¹⁰, Yen-Shen Lu¹¹, Binghe Xu¹², Yoon Sim Yap¹³, Anita Bustam¹⁴, Bin Yao¹⁵, Bo Zhang¹⁵, Richard Bryce¹⁵, Arlene Chan¹⁶

Affiliations

¹ Department of Breast Oncology, Aichi Cancer Center, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.
² Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, 540-0006, Japan.
³ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KS013, Korea.
⁴ Division of Breast Oncology, Saitama Cancer Center, Saitama, 362-0806, Japan.
⁵ Hakuaikai Medical Corporation Sagara Hospital, Kagoshima City, 892-0845, Japan.
⁶ Department of Breast Oncology, Jichi Medical University Hospital, Tochigi, 329-0498, Japan.
⁷ Department of Medicine, Queen Mary Hospital, Hong Kong Island, Hong Kong.
⁸ Department of Breast Surgery, Hiroshima City Hospital, Hiroshima, 730-8518, Japan.
⁹ Department of Breast Surgery, National Hospital Organization Hokkaido Cancer Center, Sapporo, Hokkaido, 063-0005, Japan.
¹⁰ Division of Breast Surgery, Chiba Cancer Center, Chiba, 260-8717, Japan.
¹¹ National Taiwan University Hospital, Taipei City, Taiwan.
¹² Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, PR China.
¹³ Division of Medical Oncology, National Cancer Centre Singapore, 169610, Singapore.
¹⁴ Clinical Oncology Unit, University Malaya Medical Centre, Kuala Lumpur, 50603, Malaysia.
¹⁵ Puma Biotechnology, Inc., Los Angeles, CA 90024, USA.
¹⁶ Breast Cancer Research Centre-WA & Curtin University, Perth, Australia.

PMID: 31140297
DOI: 10.2217/fon-2019-0143

Abstract

Aim: To evaluate the efficacy and safety of neratinib as extended adjuvant therapy in patients from Asia based on exploratory analyses of the Phase III ExteNET trial. Patients & methods: A total of 2840 women with early stage HER2-positive breast cancer were randomly assigned to neratinib 240 mg/day or placebo for 1 year after trastuzumab-based adjuvant therapy. Results: A total of 341 patients were from Asia (neratinib, n = 165; placebo, n = 176). 2-year invasive disease-free survival rates were 92.8 and 90.8% with neratinib and placebo, respectively (HR: 0.70; 95% CI: 0.31-1.55), and 5-year rates were 91.9 and 87.2%, respectively (HR: 0.57; 95% CI: 0.27-1.13). Diarrhea was the most common adverse event with neratinib. Conclusion: Extended adjuvant therapy with neratinib reduces disease recurrences in Asian women with HER2-positive breast cancer. Trial registration: Clinicaltrials.gov NCT00878709.

Keywords: Asia; HER2; early stage breast cancer; efficacy; extended adjuvant therapy; neratinib; safety; tyrosine kinase inhibitor.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial

MeSH terms

Aged
Aged, 80 and over
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / adverse effects
Antineoplastic Agents / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Breast Neoplasms / drug therapy*
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Chemotherapy, Adjuvant
Female
Humans
Kaplan-Meier Estimate
Middle Aged
Neoplasm Staging
Prognosis
Proportional Hazards Models
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / adverse effects
Protein Kinase Inhibitors / therapeutic use*
Quinolines / administration & dosage
Quinolines / adverse effects
Quinolines / therapeutic use*
Receptor, ErbB-2 / metabolism*
Retreatment
Trastuzumab / administration & dosage
Treatment Outcome

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Quinolines
Receptor, ErbB-2
neratinib
Trastuzumab

Associated data

ClinicalTrials.gov/NCT00878709