Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis

Background: The aim of this review was to systematically evaluate the safety and efficacy of the addition of pertuzumab to trastuzumab emtansine (T-DM1) +/- taxane in patients with human epidermal growth factor receptor 2 (HER2)-positive, locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). Materials and methods: Several databases were searched for relevant clinical trials. The study characteristics, details of adverse events (AEs) and details of treatment efficacy were extracted for analysis. Results: Six studies with 996 patients were included. Common AEs of T-DM1 + pertuzumab +/- taxane included fatigue, diarrhea, nausea, epistaxis, peripheral neuropathy, increased aspartate transaminase (AST), increased alanine transaminase (ALT) and thrombocytopenia. Major grade >= 3 AEs of T-DM1 + pertuzumab +/- taxane included thrombocytopenia, neutropenia, fatigue, increased ALT, anemia and peripheral neuropathy. The addition of pertuzumab to T-DM1 +/- taxane led to higher risks of diarrhea (especially grade >= 3 diarrhea), rash and vomiting, and decreased risks of thrombocytopenia and grade >= 3 increased AST. The relative risks of the addition of pertuzumab to T-DM1 +/- taxane for objective response (1.068, 95% CI 0.945-1.207) and clinical benefit (1.038, 95% CI 0.974-1.106) were not statistically significant. Conclusion: Common AEs should be carefully monitored in HER2-positive LABC or MBC patients treated with T-DM1 + pertuzumab +/- taxane. The addition of pertuzumab to T-DM1 +/- taxane showed noninferior, but not superior, objective response rate and clinical benefit rate. However, more studies are needed to further verify these findings.