Optimal alternative therapy for metastatic HER2-positive breast cancer progression who previously received trastuzumab-based therapy: a systematic review and network meta-analysis

Abstract Background: Trastuzumab remains the standard protocol recommended for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). After disease progression, the decision to continue trastuzumab treatment in combination with another type of chemotherapy, or to replace it with another HER2-targeted therapy, has not been conclusive. Methods: We systematically searched databases and extracted data from randomized controlled trials (RCTs) on patients who experienced disease progression after receiving trastuzumab-based therapies. Paired meta-analyses were performed to provide a comparison between patients continuously received trastuzumab-based therapy and those receiving other targeted therapies. Bayesian network meta-analysis was used to synthesize available evidence of direct or indirect comparison. Results: The 10 selected articles that included 3,158 patients were analyzed. The paired meta-analysis showed a 29% (hazard ratio (HR): 0.71; 95% confidence interval (CI): 0.60–0.85) reduction in mortality risk for patients continued receiving trastuzumab-based therapy than those receiving other targeted regimen. Bayesian network meta-analysis suggested that pertuzumab and trastuzumab plus capecitabine (PHC) showed an improvement in the overall survival (OS), with the highest surface under the cumulative ranking (SUCRA) (0.962 (82.3%)). In terms of progression-free survival (PFS) and objective response rate (ORR), trastuzumab emtansine (T-DM1) showed the highest SUCRA (0.949 (73.2%) and 0.997 (98.5%), respectively). Conclusions：Continuing trastuzumab with another type of chemotherapy is a better option for patients who experience disease progression after receiving trastuzumab-based therapy. Patients treated with PHC had the highest OS. Meanwhile, patients treated with T-DM1 showed better PFS and ORR than those treated with other regimens.