The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C.

Abstract

BACKGROUND:

Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy.

METHODS:

Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models.

RESULTS:

AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89-1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80-1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86-1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77-1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3-4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology.

CONCLUSION:

For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.

• Authors: Amelie de Gregorio, Wolfgang Janni, Thomas W P Friedl, Ulrike Nitz, Brigitte Rack, Andreas Schneeweiss, Ronald Kates, Tanja Fehm, Hans Kreipe, Matthias Christgen, Sherko Kümmel, Elisabeth Trapp, Rachel Wuerstlein, Andreas Hartkopf, Michael Clemens, Toralf Reimer, Lothar Häberle, Peter A Fasching, Oleg Gluz, Nadia Harbeck
• Journal: British journal of cancer (Br J Cancer) Vol. 126 Issue 12 Pg. 1715-1724 (06 2022) ISSN: 1532-1827 [Electronic] England
• PMID: 35194193 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Anthracyclines
• Antibiotics, Antineoplastic
• Bridged-Ring Compounds
• Taxoids
• taxane
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Anthracyclines (administration & dosage)
• Antibiotics, Antineoplastic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, enzymology, pathology)
• Bridged-Ring Compounds (administration & dosage)
• Chemotherapy, Adjuvant
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Female
• Humans
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (metabolism)
• Taxoids (administration & dosage)