Meta-analysis of Outcomes With Dose-Intense Adjuvant Chemotherapy in Early Breast Cancer
In a patient-level meta-analysis reported in The Lancet, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) found that an increased dose intensity of adjuvant taxane and anthracycline chemotherapy in early breast cancer was associated with a decreased risk of recurrence and death from breast cancer.
Study Details
The meta-analysis involved data from 37,298 women enrolled in 26 trials that compared every-2-week vs standard every-3-week schedules and trials comparing sequential full-dose vs concurrent lower-dose regimens of anthracycline and taxane chemotherapy. The primary outcomes of interest were recurrence and breast cancer mortality.
Analyses were stratifed by age, nodal status, and trial. Most women were aged < 70 years and had node-positive disease. Total cytotoxic drug usage was generally comparable in the treatment arms in each trial. Colony-stimulating factor generally was used more frequently in the dose-intense arm.
Recurrence and Breast Cancer Mortality
An analysis of combined data from all 26 trials showed that dose-intense vs standard-schedule chemotherapy was associated with a lower 10-year risk of recurrence (28.0% vs 31.4%, rate ratio [RR] = 0.86; P < .0001), breast cancer mortality (18.9% vs 21.3%, RR = 0.87; P < .0001), and all-cause mortality (22.1% vs 24.8%, RR = 0.87; P < .0001).
Reductions in the risk of recurrence at 10 years were observed among:
- 10,004 patients in 7 trials comparing every-2-week chemotherapy vs the same chemotherapy given every 3 weeks (24.0% vs 28.3%, RR = 0.83; P < .0001),
- 11,028 women in 6 trials comparing sequential vs concurrent anthracycline plus taxane chemotherapy (28.1% vs 31.3%, RR = 0.87; P = .0006), and
- 6,532 women in 6 trials evaluating both dose-intense strategies of shorter intervals and sequential administration (30.4% vs 35.0%, RR = 0.82; P < .0001).
Reductions in the risk of recurrence with dose-intense treatment were similar and significant (P < .0001) in estrogen receptor–positive and estrogen receptor–negative disease and did not differ significantly according to other patient or disease characteristics.
The investigators concluded, “Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.”
The corresponding author for The Lancet article is the EBCTCG Secretariat, Clinical Trial Service Unit, Nuffield Department of Population Health, Oxford.
Disclosure: The study was funded by Cancer Research UK and the Medical Research Council. The study authors' full disclosures can be found at thelancet.com.
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