Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52/ATHENE trial

The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. In the randomized phase 2 trial ABCSG-52 (EudraCT no. 2019-002364-27), we investigated epirubicin plus immunotherapy in women with human epidermal growth factor receptor 2 (HER2)-positive EBC. A total of 58 patients were randomized 1:1 to two cycles of a chemotherapy-free induction phase (part 1) of dual HER2 blockade with trastuzumab and pertuzumab (TP) plus the anti-programmed death ligand 1 antibody atezolizumab (TP-A) or TP alone. Thereafter, all patients received four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint, pathological complete response (pCR), was met in 35 patients (60.3%; 95% confidence interval (CI) 47.5% to 71.9%), 19 patients (65.5%) in the TP-A group and 16 patients (55.2%) in the TP group. The residual cancer burden 0/I rate and objective response rate (secondary endpoints) in all patients with evaluable data were 80.0% (n = 44/55; 95% CI 67.6% to 88.4%) and 89.3% (n = 50/56; 95% CI 78.5% to 95.0%), respectively. Grade ≥3 adverse events were reported in 17 patients (29.3%). Based on our findings, we conclude that a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab and epirubicin is effective and safe in patients with HER2-positive EBC.

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Publication Details

Journal
Nature Cancer
Published
2025-01-16
DOI
https://doi.org/10.1038/s43018-024-00890-2
Citations
6
Primary Topic
HER2/EGFR in Cancer Research
Type
article
Field-Weighted Citation Impact
6.27

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article

Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52/ATHENE trial

Florian Posch, Renate Pusch, Lukas Weiß, Dominik Hlauschek et al.
6 citations
Nature Cancer
HER2/EGFR in Cancer Research
6.27
article

Neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in women with early HER2-positive breast cancer: the randomized phase 2 ABCSG-52/ATHENE trial

Florian Posch, Renate Pusch, Lukas Weiß, Dominik Hlauschek, Ursula Denison, Christian Fridolin Singer, Zsuzsanna Bagó-Horváth, Michael Knauer, Vesna Bjelic‐Radisic, Michael Gnant, Andreas Petzer, Martin Filipits, Lidija Sölkner, Simon Peter Gampenrieder, Christine Brunner, Richard Greil, Clemens A. Schmitt, Rupert Bartsch, Nadja Zaborsky, Karl Sotlar, Daniel Egle, Verena Wieser, Maximilian Marhold, Carmen Albertini, Gabriel Rinnerthaler, Marija Balić, Edgar Petru, Bruno Schneeweiß, Magdalena Ritter, Manuela Gili
article en
6 citations

Abstract

The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. In the randomized phase 2 trial ABCSG-52 (EudraCT no. 2019-002364-27), we investigated epirubicin plus immunotherapy in women with human epidermal growth factor receptor 2 (HER2)-positive EBC. A total of 58 patients were randomized 1:1 to two cycles of a chemotherapy-free induction phase (part 1) of dual HER2 blockade with trastuzumab and pertuzumab (TP) plus the anti-programmed death ligand 1 antibody atezolizumab (TP-A) or TP alone. Thereafter, all patients received four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint, pathological complete response (pCR), was met in 35 patients (60.3%; 95% confidence interval (CI) 47.5% to 71.9%), 19 patients (65.5%) in the TP-A group and 16 patients (55.2%) in the TP group. The residual cancer burden 0/I rate and objective response rate (secondary endpoints) in all patients with evaluable data were 80.0% (n = 44/55; 95% CI 67.6% to 88.4%) and 89.3% (n = 50/56; 95% CI 78.5% to 95.0%), respectively. Grade ≥3 adverse events were reported in 17 patients (29.3%). Based on our findings, we conclude that a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab and epirubicin is effective and safe in patients with HER2-positive EBC.

Nature CancerVol. 6(1)
Johannes Kepler University of Linz (AT), Innsbruck Medical University (AT), University of Salzburg (AT), Universität Innsbruck (AT), Medical University of Graz (AT), Paracelsus Medical University (AT), Comprehensive Cancer Center Vienna (AT), Kepler Universitätsklinikum (AT), Helios Universitätsklinikum Wuppertal (DE), Breast Center (CH), Austrian Breast & Colorectal Cancer Study Group (AT), Karl Landsteiner Society (AT), Medical University of Vienna (AT)
Roche
Openalex Percentile: Top 4%
HER2/EGFR in Cancer Research
6.27
DOIOpen Access PDFOpenAlex
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