In a study conducted by the Early Breast Cancer Trialists’ Collaborative Group and reported in The Lancet Oncology by Bradley et al, an individual patient data meta-analysis of randomized trials has shown that the addition of adjuvant trastuzumab to chemotherapy reduces the risk of disease recurrence and breast cancer mortality in women with early HER2-positive breast cancer.
Study Details
The meta-analysis included data on 13,864 women with node-negative or -positive disease from seven trials (FinHER, NSABP B-31, NCCTG N9831, HERA, PACS 04, BCIRG 006, and NOAH) comparing trastuzumab plus chemotherapy vs the same chemotherapy that enrolled patients between February 2000 and December 2005. Primary outcomes were breast cancer recurrence, breast cancer mortality, death without recurrence, and all-cause mortality. Intention-to-treat log-rank analyses stratified by age, nodal status, estrogen receptor (ER) status, and trial were used to generate first-event rate ratios (RRs).
Key Findings
Among all patients, the mean scheduled treatment duration was 14.4 months and median follow-up was 10.7 years (interquartile range = 9.5–11.9 years).
Adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of and mortality from breast cancer by a third, with worthwhile proportional reductions irrespective of recorded patient and tumor characteristics.— Bradley et al
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The addition of trastuzumab to chemotherapy was associated with significant reductions in risk of recurrence (RR = 0.66, 95% confidence interval [CI] = 0.62–0.71, P < .0001) and death from breast cancer (RR = 0.67, 95% CI = 0.61–0.73, P < .0001). Absolute 10-year recurrence risk was reduced by 9.0%, from 31.9% to 22.9 (95% CI = 7.4%–10.7%, P < .0001) and 10-year breast cancer mortality was reduced by 6.4%, from 21.1% to 14.7% (95% CI = 4.9%–7.8%, P < .0001).
The addition of trastuzumab was associated with a significant reduction in risk of all-cause mortality (RR = 0.69, 95% CI = 0.64–0.75, P < .0001); absolute 10-year recurrence risk was reduced by 6.5%, from 23.4% to 16.8% (95% CI = 5.0%–8.0%, P < .0001). No significant difference in risk of death without recurrence was observed (RR = 0.90, 95% CI = 0.72–1.12, P = 0.35). Absolute 10-year risk was reduced by 0.4%, from 3.1% to 2.7% (95% CI = –0.3 to 1.1, P = .35).
The reduction in disease recurrence with the addition of trastuzumab was greatest in years 0 to 1 after randomization (RR = 0.53, 99% CI = 0.46–0.61), with benefit observed through years 2 to 4 (RR = 0.73, 99% CI = 0.62–0.85) and 5 to 9 (RR = 0.80, 99% CI = 0.64–1.01). Reductions in recurrence were similar irrespective of patient and tumor characteristics, including ER status. Patients with higher-risk tumors had greater absolute reductions in 5-year recurrence—ie, 5.7%, 6.8%, and 10.7% in N0, N1-3, and N4+ disease, respectively.
No significant increases in cardiovascular mortality (RR = 1.23, 95% CI = 0.73–2.06, P = .44) or deaths from new cancers at other sites (RR = 0.79, 95% CI = 0.54–1.17, P = .24) were observed with the addition of trastuzumab. More deaths unrelated to breast cancer occurred in the first year with trastuzumab plus chemotherapy (0.37% vs 0.16%, RR = 2.15, 95% CI = 1.11–4.14, P = .023); the excess was not found to be attributable to any particular cause of death.
The investigators concluded, “Adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of and mortality from breast cancer by a third, with worthwhile proportional reductions irrespective of recorded patient and tumor characteristics.”
EBCTCG Secretariat, at the Clinical Trial Service Unit, Nuffield Department of Population Health, Oxford, is the corresponding entity for The Lancet Oncology article.
Disclosure: The study was funded by Cancer Research UK and UK Medical Research Council. For full disclosures of the study authors, visit thelancet.com.
