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.