As reported in The Lancet by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), a patient-level meta-analysis showed that anthracycline/taxane regimens were associated with better outcomes compared with regimens excluding either drug class in patients with early-stage operable breast cancer.
As stated by the authors, “Anthracycline–taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy.”
The analysis included data on 18,103 patients from 15 adjuvant or neoadjuvant trials of taxane regimens with or without anthracycline that provided patient-level data, and as well as data on 52,976 patients from 35 trials of anthracycline regimens with or without taxane that provided patient-level data.
Across all 15 trials of taxane with vs without anthracycline, recurrence rates were 14% lower on average (rate ratio [RR] = 0.86, 95% confidence interval [CI] = 0.79–0.93, P = .0004) with taxane regimens including anthracycline vs those without anthracycline. Non–breast cancer deaths were not increased with taxane/anthracycline regimens, but 1 additional case of acute myeloid leukemia per 700 patients was observed. The greatest reduction in recurrence risk was found with concurrent anthracycline plus docetaxel/cyclophosphamide vs the same dose of docetaxel plus cyclophosphamide without anthracycline (10-year recurrence risk = 12.3% vs 21.0%, RR = 0.58, 95% CI = 0.47–0.73, P < .0001); 10-year breast cancer mortality was reduced by 4.2% (95% CI = 0.4%–8.1%, P = .0034) in this comparison. No significant reduction in recurrence risk was found for sequential schedules of taxane plus anthracycline vs docetaxel/cyclophosphamide (RR = 0.94, 95% CI = 0.83–1.06, P = .30).
Across the 35 trials of anthracycline regimens with vs without taxane, larger reductions in recurrence risk were observed in trials adding taxane to anthracycline regimens when the cumulative dose of anthracycline was the same in each group (RR = 0.87, 95% CI = 0.82–0.93, P < .00017) compared with trials with twofold higher cumulative doses of nontaxane (mostly anthracycline) regimens in the control group vs the taxane/anthracycline group (RR = 0.96, 95% CI = 0.90–1.03, P = .27).
Direct comparisons between anthracycline and taxane regimens showed that higher cumulative dose and more dose-intense schedules were more efficacious. Proportional reductions in recurrence risk for taxane/anthracycline were similar in estrogen receptor (ER)-positive and ER-negative disease and showed no differences according to age, nodal status, or tumor size or grade.
The investigators concluded: “Anthracycline plus taxane regimens are most efficacious at reducing breast cancer recurrence and death. Regimens with higher cumulative doses of anthracycline plus taxane provide the greatest benefits, challenging the current trend in clinical practice and guidelines towards non-anthracycline chemotherapy, particularly shorter regimens, such as four cycles of docetaxel–cyclophosphamide. By bringing together data from almost all relevant trials, this meta-analysis provides a reliable evidence base to inform individual treatment decisions, clinical guidelines, and the design of future clinical trials.”
EBCTCG Secretariat, Clinical Trial Service Unit, Nuffield Department of Population Health, Oxford, UK, is the corresponding entity for The Lancet article.
Disclosures: The study was funded by Cancer Research UK and UK Medical Research Council. For full disclosures of the study authors, visit www.thelancet.com.
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