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Meta-Analysis
. 2024 Jul;13(14):e70005.
doi: 10.1002/cam4.70005.

Concurrent epirubicin and trastuzumab use increases complete pathological response rate without additional cardiotoxicity in patients with human epidermal growth factor receptor 2-positive early breast cancer: A meta-regression analysis

Ming-Han Yang  1 , Chiun-Sheng Huang  2   3 , Dwan-Ying Chang  1 , Fu-Chang Hu  4   5 , Shu-Min Huang  1 , Po-Hsiang Huang  1 , I-Chun Chen  1   6   7 , Tom Wei-Wu Chen  1   7 , Ching-Hung Lin  1   3   6 , Yen-Shen Lu  1   3
Affiliations
Meta-Analysis

Concurrent epirubicin and trastuzumab use increases complete pathological response rate without additional cardiotoxicity in patients with human epidermal growth factor receptor 2-positive early breast cancer: A meta-regression analysis

Ming-Han Yang et al. Cancer Med. 2024 Jul.

Abstract

Background: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC).

Methods: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta-regression analyses to investigate the effects of multiple covariates.

Results: We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68-2.05). Compared with nonconcurrent or non-anthracycline-containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04-2.12). The linear fixed-effects meta-regression analysis indicated that in trials including more patients with hormone receptor-positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant.

Conclusions: The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR-negative, HER2-positive tumors to enhance pCR rates, with caution advised for HR-positive tumors due to potential cardiotoxicity.

Keywords: cardiotoxicity; early breast cancer; epirubicin; human epidermal growth factor receptor 2; trastuzumab.

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Conflict of interest statement

Dr. Lu reports consulting and speaker fees from Novartis, Pfizer, Roche, and Merck Sharp & Dohme and study grants from Novartis, Roche, and Merck Sharp & Dohme. The other authors have no related conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram of systematic literature search and trial selection process.
FIGURE 2
FIGURE 2
The forest plot of cardiotoxicity. A random‐effects meta‐analysis of the cardiotoxicity in concurrent epirubicin–trastuzumab regimens and nonconcurrent regimens was shown here. “Experiment” refers to the concurrent epirubicin–trastuzumab regimens and “Control” refers to the nonconcurrent regimens. An RR = 1 indicated no difference between the treatments, an RR <1 indicated that the concurrent regimen of epirubicin and trastuzumab was associated with relatively low cardiotoxicity, and an RR >1 indicated that the control regimen was better in this regard.
FIGURE 3
FIGURE 3
The forest plot of pathological complete response (pCR) rates. A random‐effects meta‐analysis of the pCR rate in concurrent epirubicin–trastuzumab regimens and nonconcurrent regimens was shown here. “Experiment” refers to the concurrent epirubicin–trastuzumab regimens and “Control” refers to the nonconcurrent regimens. An OR >1 indicated that the concurrent regimen of epirubicin and trastuzumab was associated with a higher pCR rate.
See this image and copyright information in PMC

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