Effect and safety of dual anti-human epidermal growth factor receptor 2 therapy compared to monotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer: a systematic review.

Xiao Zhang,Fei-Fei Yu,Xin-Ji Zhang,Jia He,Ye-Sheng Li,Tian-Yi Zhang,Xin Wei

doi:10.1186/1471-2407-14-625

Abstract

BackgroundDual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. We undertook a systematic review to compare treatment outcomes for patients who received single or combined anti-HER2 therapies.MethodsWe identified randomized control trials that compared dual anti-HER2 therapy and anti-HER2 monotherapy in patients with HER2-positive breast cancer. Outcomes included pathologic complete response (pCR), overall survival (OS), progression-free survival (PFS), and adverse events. Included in the analysis were seven trials that recruited 2,609 patients.ResultsIn the neoadjuvant setting, the pooled pCR rate in the dual anti-HER2 therapy and monotherapy groups in combination with chemotherapy was 54.8% and 36%, respectively. This difference was statistically significant (relative risk, 1.56; 95% confidence interval (CI), 1.23–1.97; p < 0.001). In the metastatic setting, dual anti-HER2 therapy demonstrated significant benefits in both PFS (hazard ratio (HR), 0.71; 95% CI, 0.62–0.81; p < 0.001) and OS (HR, 0.68; 95% CI, 0.57–0.82; p < 0.001). Subgroup analyses indicated that the addition of chemotherapy to dual anti-HER2 therapy could greatly improve pCR in the neoadjuvant settings. However, in the metastatic setting, similar PFS and OS were found in patients receiving dual anti-HER2 therapy with or without chemotherapy. Dual anti-HER2 therapy was associated with more frequent adverse events than monotherapy, but no statistical differences were observed in cardiac toxicity.ConclusionsThis systematic review provides a summary of all the data currently available, and confirms the benefits and risks of dual anti-HER2 therapy for HER2-positive breast cancer.

Highlights

Dual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients
The role of dual anti-HER2 therapy in the neoadjuvant setting was evaluated in five trials [21,25,26,27,28] and two trials [15,24] investigated dual antiHER2 therapy in the metastatic setting
We found that the benefit of dual anti-HER2 therapy on pathologic complete response (pCR) was similar among different chemotherapies

Summary

Introduction

Dual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. Lapatinib, an anti-HER2 tyrosine kinase inhibitor, was approved for use, in combination with capecitabine, for the treatment of HER2-positive metastatic breast cancer that has progressed with standard treatment [9,10] Despite these improvements, resistance to these drugs remains a challenge, and novel therapeutic approaches are required [11,12]. The addition of pertuzumab, an anti-HER2 monoclonal antibody, to trastuzumab and docetaxel therapy significantly increases progression-free survival (PFS) for patients with HER2-positive metastatic breast cancer (median PFS, 19.5 versus 12.4 months) [15] These impressive results have provided a strong rationale for conducting randomized controlled studies evaluating trastuzumab in combination with lapatinib or pertuzumab for HER2-positive breast cancer in both the adjuvant and metastatic settings. We conduct a systematic review of these RCTs to summarize the benefits and risks of dual anti-HER2 therapy, as compared with monotherapy, for HER2-positive breast cancer patients

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