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Anthracycline- and Taxane-containing Chemotherapy for Early-Stage Operable Breast Cancer

Favorable results for anthracycline-taxane regimens for early-stage operable breast cancer challenges “the current trend in clinical practice and guidelines towards non-anthracycline chemotherapy, particularly shorter regimens, such as four cycles of docetaxel–cyclophosphamide,” authors conclude. The patient-level meta-analysis of 100,000 women from 86 randomized trials shows: “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.… 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.”

The patient-level meta-analysis included 100,000 women from 86 randomized trials, including 15 trials of taxane regimens with or without anthracycline in 18,103 women . Based on primary outcomes of breast cancer recurrence and cause-specific mortality, the researchers report: “Across all 15 trials that provided individual data, recurrence rates were 14% lower on average (RR 0.86, 95% CI 0.79–0.93; P = 0.0004) with taxane regimens including anthracycline than those without. Non-breast cancer deaths were not increased but there was one additional acute myeloid leukaemia case per 700 women treated. The clearest reductions in recurrence were found when anthracycline was added concurrently to docetaxel plus cyclophosphamide versus the same dose of docetaxel plus cyclophosphamide (10-year recurrence risk 12.3% vs 21.0%; risk difference 8.7%, 95% CI 4.5–12.9; RR 0.58, 0.47–0.73; P <0.0001). 10-year breast cancer mortality in this group was reduced by 4.2% (0.4–8.1; P = 0.0034). No significant reduction in recurrence risk was found for sequential schedules of taxane plus anthracycline when compared with docetaxel plus cyclophosphamide (RR 0.94, 0.83–1.06; P = 0.30).”

In 35 trials of anthracycline regimens with versus without taxane, data for 52,976 women showed the following: “Larger recurrence reductions were seen from adding taxane to anthracycline regimens when the cumulative dose of anthracycline was the same in each group (RR 0.87, 0.82–0.93; P <0.0001; n = 11,167) than in trials with two-fold higher cumulative doses of non-taxane (mostly anthracycline) in the control group than in the taxane group (RR 0.96, 0.90–1.03; P = 0.27; n = 14,620). Direct comparisons between anthracycline and taxane regimens showed that a higher cumulative dose and more dose-intense schedules were more efficacious. The proportional reductions in recurrence for taxane plus anthracycline were similar in oestrogen receptor-positive and oestrogen receptor-negative disease, and did not differ by age, nodal status, or tumour size or grade.”

Source: Lancet