Trastuzumab-pertuzumab combined with taxanes or eribulin in HER2-positive breast cancer: A single-arm meta-analysis of RCTs.

Abstract

e13019 Background: Trastuzumab-pertuzumab combined with taxanes or eribulin has emerged as a promising therapeutic regimen for HER2-positive breast cancer, a subtype known for its aggressive clinical course. This single-arm meta-analysis of randomized controlled trials aims to evaluate the efficacy and safety of these combinations, providing evidence to guide treatment strategies for this challenging malignancy. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane, and Scopus using relevant keywords from inception till January 2025. Statistical pooling was executed using OpenMeta Software (version 5.3). Occurrence rates, presented as untransformed proportions, were pooled with the corresponding 95% confidence interval using a random-effects model. Interstudy heterogeneity was evaluated using the I² and χ² statistics, with I² > 50% being considered as significant. Results: Sixteen studies yielding 3300 patients were included. An overall mortality rate of 25.7% among patients who received prior neoadjuvant or adjuvant systemic therapy was revealed (95% CI = 0.13-0.41, I = 97.6%, p < 0.001) while those who did not get prior therapy exhibited a mortality rate of 45% (95% CI: 0.34-0.57, I = 94.38%, p < 0.001). 9.6% deaths were reported for subjects less than 65 years (95% CI: 0.05-0.16, I = 81.5%, p < 0.001) and 12.4% for subjects above 65 years (95% CI: 0.06-0.21, I = 81.68%, p < 0.001). The pooled disease-free interval was 17.92 months (95% CI: 14.52–21.32, I = 99.86%, p < 0.001). The overall tumor objective response rate was estimated at 76.5% (95% CI: 0.65-0.85, I = 92.72%, p < 0.001). The pooled analysis revealed the following adverse events: Alopecia in 70% (95% CI: 0.48-0.88, I = 95.75%, p < 0.001), anemia in 29% (95% CI: 0.09-0.55, I = 96.75, p < 0.001), diarrhea in 50% (95% CI: 0.37-0.63, I = 96.18%, p < 0.001), dry skin in 40% (95% CI: 0.14-0.71, I = 97.53, p < 0.001), fatigue in 71% (95% CI: 0.36-0.96, I = 96.69, p < 0.001), febrile neutropenia in 8% (95% CI: 0.03-0.15, I = 89.57, p < 0.001), hypertension in 11% (95%CI: 0.02-0.29, I = 95.15, p < 0.001), left ventricular dysfunction in 24% (95%CI: 0.14-0.36, I = 78.91%,p < 0.009), mucositis in 24% (95% CI: 0.14-0.36, I = 78.91%,p < 0.009), nail disorders in 14% (95%CI: 0.07-0.23, I = 0%,p = 0.76), nausea in 44% (95%CI: 0.31-0.59, I = 90.18%, p < 0.001), neutropenia in 35% (95%CI: 0.24-0.48, I = 95.68%,p < 0.001), peripheral neuropathy in 33% (95%CI: 0.09-0.64, I = 98.68,p < 0.001). Conclusions: This meta-analysis highlights the differential mortality rates and a spectrum of adverse events associated with trastuzumab-pertuzumab combined with taxanes or eribulin in HER2-positive breast cancer patients, influenced by prior therapy status and age. These findings underscore the need for personalized treatment strategies to optimize efficacy and manage toxicities effectively.