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Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer : Results from the phase 3 PANTHER trial

Papakonstantinou, Antroula ; Matikas, Alexios ; Bengtsson, Nils Olof ; Malmström, Per LU ; Hedayati, Elham ; Steger, Guenther ; Untch, Michael ; Hübbert, Laila ; Johansson, Hemming and Hellström, Mats , et al. (2020) In Cancer 126(6). p.1175-1182
Abstract

Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)–positive disease. Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive... (More)

Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)–positive disease. Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse–free survival. In addition, HER2-positive patients and an equal number of HER2-negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow-up. Results: There were 342 HER2-positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse-free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37-1.27; P =.231). Cardiac outcomes after 4 and 6 years of follow-up did not differ significantly between HER2-positive and HER2-negative patients or between the 2 treatment groups. Conclusions: The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
adjuvant chemotherapy, breast cancer, cardiotoxicity, dose-dense, human epidermal growth factor receptor 2 (HER2), trastuzumab
in
Cancer
volume
126
issue
6
pages
8 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:31851385
  • scopus:85076880892
ISSN
0008-543X
DOI
10.1002/cncr.32653
language
English
LU publication?
yes
id
5024fb5f-28e1-4f9a-96ee-0990a4dc7a81
date added to LUP
2020-04-16 13:59:15
date last changed
2022-09-24 05:41:38
@article{5024fb5f-28e1-4f9a-96ee-0990a4dc7a81,
  abstract     = {{<p>Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)–positive disease. Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse–free survival. In addition, HER2-positive patients and an equal number of HER2-negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow-up. Results: There were 342 HER2-positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse-free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37-1.27; P =.231). Cardiac outcomes after 4 and 6 years of follow-up did not differ significantly between HER2-positive and HER2-negative patients or between the 2 treatment groups. Conclusions: The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies.</p>}},
  author       = {{Papakonstantinou, Antroula and Matikas, Alexios and Bengtsson, Nils Olof and Malmström, Per and Hedayati, Elham and Steger, Guenther and Untch, Michael and Hübbert, Laila and Johansson, Hemming and Hellström, Mats and Gnant, Michael and Loibl, Sibylle and Greil, Richard and Moebus, Volker and Foukakis, Theodoros and Bergh, Jonas}},
  issn         = {{0008-543X}},
  keywords     = {{adjuvant chemotherapy; breast cancer; cardiotoxicity; dose-dense; human epidermal growth factor receptor 2 (HER2); trastuzumab}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{6}},
  pages        = {{1175--1182}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Cancer}},
  title        = {{Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer : Results from the phase 3 PANTHER trial}},
  url          = {{http://dx.doi.org/10.1002/cncr.32653}},
  doi          = {{10.1002/cncr.32653}},
  volume       = {{126}},
  year         = {{2020}},
}