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Benefit from dose-dense adjuvant chemotherapy for breast cancer: subgroup analyses from the randomised phase 3 PANTHER trial

Year: 2024
Type: article
Abstract: Background: It is unclear whether some patients with high-risk breast cancer do not warrant adjuvant dose-dense chemotherapy due to small expected absolute benefit. Methods: The phase 3 PANTHER trial (NCT00798070) compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose-dense (tDD EC/D) or standard interval schedule (FEC/D) to patients with high-risk resected early breast cancer (n = 2003). We compared outcomes across key subgroups of interest, evaluated the performance of the online prognostication and treatment benefit estimation tool PREDICT and conducted a subpopulation treatment effect pattern plot (STEPP) analysis. Primary endpoint was breast cancer recurrence free survival (BCRFS). Findings: Median follow-up was 10.3 years. Treatment with tDD EC/D improved 10-year BCRFS across all subgroups including according to menopausal status, with an absolute benefit of 2% or more, as well as in luminal (Hazard Ratio [HR] = 0.83, 95% Confidence Interval [CI] 0.65-1.05) and Human Epidermal Growth Factor Receptor 2 (HER2) positive (HR = 0.53, 95% CI 0.30-0.93), but not triple negative breast cancer patients (HR = 1.02, 95% CI 0.66-1.57). PREDICT underestimated overall survival in the entire population and across all subgroups. In STEPP analysis, absolute benefit from tDD EC/D in BCRFS was stable across risk-defined subpopulations, from 3.8% in the lowest risk patients to 3.6% in the highest risk ones. There was no differential treatment effect over time. Interpretation: We could not reliably identify any subgroup not benefiting from dose-dense treatment, which should be considered for patients with primary resected high-risk breast cancer. Funding: Cancerfonden, Bröstcancerförbundet, Radiumhemmets Forskningsfonder, Amgen, Roche, sanofi-aventis.
DOI: 10.1016/j.lanepe.2024.101162
Authors: Alexios Matikas, Andri Papakonstantinou, Sibylle Loibl, Günther G. Steger, Michael Untch, Hemming Johansson, Nikos Tsiknakis, Mats Hellström, Richard Greil, Volker Möbus, Michael Gnant, Jonas Bergh, Theodoros Foukakis
Institutions: Karolinska University Hospital, Karolinska Institutet, German Breast Group, Medical University of Vienna, Helios Hospital Berlin-Buch, Paracelsus Medical University, Arbeitsgemeinschaft medikamentöse Tumortherapie, Goethe University Frankfurt
Language: English
Subfield: Cancer Research
Open Access status: gold
Estimated APC paid: $4,000
OpenAlex ID: W4404982635
FWCI: 1.063
Cites: 33
Cited by: 7
Related to: 10