Long-term data confirm a survival benefit with adjuvant anthracycline-taxane-based chemotherapy in early breast cancer

Cytotoxic Therapy

Updated analysis of the ABC trials favors anthracycline-based regimens in terms of IDFS and RFI, but no OS, when compared to taxane-based chemotherapy

A 6.9 follow-up of the joint analysis of the Anthracyclines in Early Breast Cancer (ABC) trials comparing the efficacy of nonanthracycline therapy to anthracycline-based regimens in the adjuvant setting for the treatment of operable early-stage breast cancer, failed to demonstrate a non-inferiority of six cycles of docetaxel with cyclophosphamide (TC6) compared to standard therapy of docetaxel or paclitaxel with cyclophosphamide and doxorubicin (TaxAC) (J Clin Oncol.2024 Feb 9:JCO2301428). However, no differences in overall survival (OS) advantage were reported for the two regimens.

Anthracyclines are still the chemotherapy backbone for (neo)adjuvant treatment of all subtypes of breast cancer although they are associated with an increased risk of cardiac toxicity and leukemia. The advent of alternative active cytotoxic agents, targeted therapies and immunotherapy have fueled the debate about de-escalating anthracyclines, and the combination of TC emerged as a promising anthracycline-free regimen in early breast cancer (J Clin Oncol. 2009 Mar 10;27(8):1177-83).

The ABC trials were three sequential adjuvant trials that randomly assigned a total of 4,181 women with early breast cancer to either receive TC6 or TaxAC. The long-term analysis of invasive disease-free survival (IDFS), the primary endpoint of the three trials, was consistent with data reported in the original analysis at 3.3 years of median follow-up (J Clin Oncol. 2017 Aug 10;35(23):2647-2655).

Five-year IDFS rates were 85.1% for TC6 and 86.7% for TaxAC, and noninferiority of the nonanthracycline regimens was not demonstrated in the intention-to-treat population on the basis of the original criteria. Recurrence-free interval (RFI), which excluded deaths not due to breast cancer as events, was a secondary endpoint and favored anthracycline-based regimens, with 295 events in the TC6 group and 216 events in the TaxAC arms (HR, 1.38; 95% CI, 1.16 to 1.65; P=5.0003). Five-year OS rates are 91.8% in the TC6 groups and 92.4% in the TaxAC groups. TaxAC significantly reduced any recurrence as a first event compared with TC6, but was associated with increased leukemias and non–breast cancer deaths.

“I do not believe that these results settle the debate around the exclusion of anthracyclines from the (neo)adjuvant treatment of breast cancer”, says Dr Philippe Aftimos, Institut Jules Bordet, Bruxelles, Belgium, commenting on the data published. “Only one of the three ABC trials allowed the use of a standard anthracycline-based regimen - i.e. adriamycin or epirubicin in combination with cyclophosphamide (x4) followed by weekly paclitaxel (x12) - which has shown an improvement in OS with dose density and has a lower cumulative dose of anthracyclines when compared to six cycles of TAC”.

In the long-term analysis, superiority for TaxAC was more pronounced in hormone receptor (HR)–negative breast cancer. “The finding about the hormone receptors is a step forward that needs definitive confirmation as TC is already a very popular regimen in the clinics for patients with node-negative HR positive/HER2 negative breast cancer with an indication for chemotherapy”, concludes Aftimos. “With the advent of novel therapies including CDK4/6 inhibitors and PARP inhibitors, and a general improvement in cure rates, efforts to identify patients that are candidates for treatment escalation or de-escalation must continue as clinical research priorities.”

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