What is the optimal first-line regimen for patients with advanced HER2-positive breast cancer: A systematic review and network meta-analysis

ABSTRACT Background: The advent of anti-HER2 agents, such as trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1), has significantly improved survival in metastatic HER2-positive breast cancer (BC). Multiple anti-HER2 combination regimens are recommended as first-line treatments, but the optimal choice remains unclear. This study aimed to determine the optimal first-line regimen for metastatic HER2-positive BC through a network meta-analysis of clinical trial data. Method: The PubMed, Embase, and Cochrane Library databases and abstracts from ASCO, ESMO, and WCLC were searched up to March 16, 2023. Eligible randomized controlled trials (RCTs) were selected to analyze the progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs). Fourteen treatment regimens were ranked using the network meta-analysis and the surface under the cumulative ranking curve. Results: Nineteen RCTs with 3,887 participants were analyzed. The taxane or paclitaxel or docetaxel + trastuzumab + pyrotinib (THPyr) regimen demonstrated the most significant PFS benefit, followed by the taxane or paclitaxel or docetaxel + trastuzumab + pertuzumab (THP) regimen. Regarding the ORR, THPyr ranked the highest, followed by THP and trastuzumab emtansin + pertuzumab (TdmP). THP offered the most favorable OS benefit. THPyr was effective in patients with HER2 3 + and hormone receptor-negative and positive status. No significant differences in safety and ≥3AEs were observed between the THPyr and other regimens. Conclusion: The THPyr regimen might be optimal as initial treatment for patients with advanced HER2-positive BC and is likely to be approved as a new first-line treatment option.