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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
Author(s) -
Papakonstantinou Antroula,
Matikas Alexios,
Bengtsson Nils Olof,
Malmström Per,
Hedayati Elham,
Steger Guenther,
Untch Michael,
Hübbert Laila,
Johansson Hemming,
Hellström Mats,
Gnant Michael,
Loibl Sibylle,
Greil Richard,
Moebus Volker,
Foukakis Theodoros,
Bergh Jonas
Publication year - 2020
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.32653
Subject(s) - medicine , trastuzumab , epirubicin , docetaxel , hazard ratio , oncology , breast cancer , clinical endpoint , cyclophosphamide , randomized controlled trial , chemotherapy , cancer , surgery , confidence interval
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.