Efficacy and Safety of Pyrotinib Versus T-DM1 in HER2+ Metastatic Breast Cancer Patients Pre-Treated With Trastuzumab and a Taxane: A Bayesian Network Meta-Analysis

Abstract

Purpose: To compare the efficacy and safety between pyrotinib (Pyr) and trastuzumab emtansine (T-DM1) in pre-treated human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients.

Methods: A comprehensive literature search of the PubMed, EMBASE, and Web of Science was performed in August 2020. Randomized clinical trials comparing the efficacy and safety between different anti-HER2 regimens in patients pre-treated with trastuzumab (Tra) and a taxane in metastatic settings (≤second-line treatment) were included. A fixed effects network meta-analysis based on the Bayesian inferential framework was conducted for progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 adverse events (AEs). Values of surface under cumulative ranking probability curve (SUCRA) were calculated to offer a ranking of all regimens.

Results: Twelve studies with 4,353 subjects were identified. Nine regimens were included into the network: T-DM1, lapatinib-capecitabine (Lap-Cap), Tra-Cap, Cap, neratinib (Ner), pertuzumab (Per)-Tra-Cap, Pyr-Cap, atezolizumab (Ate)-T-DM1, and Ner-Cap. For PFS, Pyr-Cap was more favorable than T-DM1 (hazard ratio, 95% confidence interval: 0.77, 0.70-0.86), Lap-Cap (0.64, 0.59-0.69), Tra-Cap (0.63, 0.56-0.70), Cap (0.50, 0.45-0.56), Ner (0.59, 0.51-0.69), Per-Tra-Cap (0.68, 0.59-0.79), and Ner-Cap (0.72, 0.64-0.81). For OS, Pyr-Cap showed further improvement than Lap-Cap (hazard ratio, 95% confidence interval: 0.71, 0.52-0.99), Cap (0.68, 0.49-0.96), and Ner (0.65, 0.45-0.94). For ORR, Pyr-Cap was significantly superior than Cap (odds ratio, 95% confidence interval: 7.87, 1.22-56.51). No significant difference was observed in grade ≥3 AEs among all the regimens. Pyr-Cap ranked in the highest in PFS, OS, ORR, and grade ≥3 AEs (SUCRA = 99.4, 89.7, 86.4, and 89.3%).

Conclusions: These results indicate that Pyr may be more effective than T-DM1 in HER2+ MBC patients pre-treated with Tra and a taxane. However, it may be associated with more grade ≥3 AEs.

Keywords: human epidermal growth factor; metastatic breast cancer; network meta-analysis; pyrotinib; trastuzumab emtansine.

Figure 1

PRISMA 2009 Flow Diagram of study selection process. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis; RCT, randomized controlled trial; HER2, human epidermal growth factor receptor 2-positive.

Figure 2

(A) Risk of bias graph and (B) summary. In the risk of bias graph, the length of each rectangle was proportional to the number of studies being assessed as corresponding risk of bias. In the risk of bias summary, the risk of bias of each domain in each included study was listed.

Figure 3

Network structure diagram. T-DM1, trastuzumab emtansine; Lap, lapatinib; Tra, trastuzumab; Cap, capecitabine; Ner, neratinib; Per, pertuzumab; Pyr, pyrotinib; Ate, atezolizumab.

Figure 4

League table of network meta-analysis of the nine anti-HER2 regimens. (A) PFS and (B) OS. PFS, progression-free survival; OS, overall survival; T-DM1, trastuzumab emtansine; Lap, lapatinib; Tra, trastuzumab; Cap, capecitabine; Ner, neratinib; Per, pertuzumab; Pyr, pyrotinib; Ate, atezolizumab.

Figure 5

Rank probability plot of (A) PFS and (B) OS. PFS, progression-free survival; OS, overall survival; T-DM1, trastuzumab emtansine; Lap, lapatinib; Tra, trastuzumab; Cap, capecitabine; Ner, neratinib; Per, pertuzumab; Pyr, pyrotinib; Ate, atezolizumab.

Figure 6

Surface under the cumulative ranking curves (SUCRA) for anti-HER2 regimens of all outcomes. (A) PFS (B) OS (C) ORR (D) grade ≥3 AEs. PFS, progression-free survival; OS, overall survival; ORR, overall response rate; AEs, adverse events; T-DM1, trastuzumab emtansine; Lap, lapatinib; Tra, trastuzumab; Cap, capecitabine; Ner, neratinib; Per, pertuzumab; Pyr, pyrotinib; Ate, atezolizumab.