Anti-HER2 antibody prolongs overall survival disproportionally more than progression-free survival in HER2-Positive metastatic breast cancer patients

I-Chun Chen; Fu-Chang Hu; Ching-Hung Lin; Shu-Min Huang; Dwan-Ying Chang; Ann-Lii Cheng; Yen-Shen Lu

doi:10.1016/j.breast.2021.07.006

Anti-HER2 antibody prolongs overall survival disproportionally more than progression-free survival in HER2-Positive metastatic breast cancer patients

Breast. 2021 Oct:59:211-220. doi: 10.1016/j.breast.2021.07.006. Epub 2021 Jul 8.

Authors

I-Chun Chen¹, Fu-Chang Hu², Ching-Hung Lin³, Shu-Min Huang⁴, Dwan-Ying Chang⁵, Ann-Lii Cheng³, Yen-Shen Lu⁶

Affiliations

¹ Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Graduate Institute of Clinical Medicine and School of Nursing, College of Medicine, National Taiwan University, Taipei, Taiwan; Statistical Consulting Clinic, International-Harvard (I-H) Statistical Consulting Company, Taipei, Taiwan.
³ Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
⁵ Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
⁶ Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: yslu@ntu.edu.tw.

Abstract

Background: This meta-analysis aimed to test the hypothesis that the HER2-positive metastatic breast cancer (mBC) patients treated with anti-HER2 antibodies in trial intervention arms have a greater prolongation of overall survival (OS) than of progression-free survival (PFS) and this extra-prolongation of median survival time in OS relates specifically to the anti-HER2 antibody.

Methods: The NCBI/Pubmed and Cochrane databases were searched systematically for HER2-positive or mBC trials published in English during January 1999-November 2017. Treatment arms with shorter PFS were considered as the "control" arm, whereas those with longer PFS as the "test" arm. The between-treatment drug differences were grouped into nine categories. Groups with or without anti-HER2 antibodies were pooled respectively for comparisons. The interrelationships between PFS and OS hazard ratios (HRs) and median survival time differences were investigated by conducting fixed-effects and mixed-effects linear meta-regression analyses.

Results: Twenty-eight trials (10,928 patients) from 438 articles were collected, and four with missing data were excluded in meta-regression analysis. Overall median PFS (HR = 0.73, 95% CI: 0.68-0.78) and median OS (HR = 0.82, 95% CI: 0.77-0.87) weakly favored the longer PFS arm with a weak correlation between the PFS and OS HRs. However, the between-treatment drug difference was anti-HER2 antibody, the absolute increment in median OS time was double that of median PFS time (p < 0.001) and linearly correlated, which was not found with any non-anti-HER2 antibody drug differences.

Conclusions: Anti-HER2 antibody in patients with HER2-positive mBC prolonged OS more than PFS and mandates further investigation.

Keywords: HER2; Metastatic breast cancer; Overall survival; Progression-free survival.

Publication types

Meta-Analysis

MeSH terms

Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms* / drug therapy
Disease-Free Survival
Female
Humans
Progression-Free Survival
Receptor, ErbB-2
Trastuzumab / therapeutic use

Substances

Receptor, ErbB-2
Trastuzumab