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Evidence summaries

Trastuzumab Containing Regimens for Early Breast Cancer

Trastuzumab added to chemotherapy significantly improves overall survival (OS) and disease free survival (DFS) in HER2-positive women with early breast cancer. However, it increases the risk of congestive heart failure. Level of evidence: "A"

Summary

A Cochrane review [Abstract] 1 included 8 studies with a total of 11 991 patients to assess the efficacy and safety of therapy with trastuzumab with the standard chemotherapy regimen in patients with HER2-positive early breast cancer.

OutcomeNumber of participants (studies)Assumed risk(moderate risk-control)Corresponding risk(trastuzumab)Relative effect (95% CI)Quality of evidence (GRADE)
Overall survival (OS)9945 (8)300 per 1000210 per 1000(184 to 240)HR 0.66 (0.57 to 0.77)high
Disease free survival (DFS)9935(8)300 per 1000193 per 100(163 to 224)HR 0.6 (0.5 to 0.71)high
Congestive heart failure10281(8)20 per 1000102 per 1000(60 to 174)RR 5.11 (3 to 8.72)high
Left ventricular ejection fraction (LVEF) decline7939(7)30 per 100055 per 1000(41 to 74)RR 1.83 (1.36 to 2.47)moderate
Brain metastasis as first relapse6881(5)13 per 100023 per 1000(17 to 32)RR 1.75 (1.29 to 2.38)low

The results of the intervention and control groups are presented assuming moderate baseline risk in the control group. These absolute differences were obtained using the HR of overall survival (OS) and disease free survival (DFS) estimated in the meta-analysis. The absolute differences in safety were obtained using their RRs, estimated in the meta-analysis.

Another meta-analysis 3 included 7 randomised trials with a total of 13 864 patients. Mean scheduled treatment duration was 14.4 months and median follow-up was 10.7 years. The risks of breast cancer recurrence (RR 0.66, 95% CI 0.62 to 0.71; p<0.0001) and death from breast cancer (0.67, 0.61 to 0.73; p<0.0001) were lower with trastuzumab plus chemotherapy than with chemotherapy alone. Absolute 10-year recurrence risk was reduced by 9.0% (p<0·0001) and 10-year breast cancer mortality was reduced by 6.4% (p<0·0001), with a 6.5% reduction in all-cause mortality, and no increase in death without recurrence. Proportional recurrence reductions were similar irrespective of recorded patient and tumour characteristics, including ER status. The more high risk the tumour, the larger the absolute reductions in 5-year recurrence.

Clinical comments

Note

Date of latest search: 2022-01-03

References

  • Moja L, Tagliabue L, Balduzzi S et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 2012;4:CD006243. [PubMed]
  • Early Breast Cancer Trialists' Collaborative group (EBCTCG).. Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol 2021;22(8):1139-1150. [PubMed]

Primary/Secondary Keywords