Comparison of pathological complete response (pCR) between short-term (<6 cycles) and long-term (≥6 cycles) neoadjuvant trastuzumab therapy for HER2-positive breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Background: Human epidermal growth factor receptor 2 (HER2) positive breast cancer is a distinct molecular subtype. Trastuzumab-based neoadjuvant therapy (NAT) (combined with chemotherapy and/or additional anti-HER2 agents) is the standard of care, but the optimal duration of trastuzumab cycles (short-term: <6 vs. long-term: ≥6) remains controversial. This meta-analysis aims to comprehensively evaluate the efficacy and safety of long-term (≥6 cycles) and short-term (<6 cycles) neoadjuvant trastuzumab treatment for HER2-positive breast cancer.

Methods: The PubMed, EMBASE, and Web of Science databases were systematically searched to include randomized controlled trials (RCTs) comparing long-term and short-term neoadjuvant trastuzumab treatment for HER2 positive breast cancer. The primary outcome measurement was the pathological complete response (pCR) rate, and the secondary outcome measurement was the incidence of adverse events. RevMan and STATA software were used for meta-analysis.

Results: A total of five RCTs involving 799 patients were included. The meta-analysis showed that there was no significant difference in pCR between long-term and short-term treatment [risk ratio (RR) =0.78, 95% confidence interval (CI): 0.60-1.02; P=0.07; I²=62%], but long-term treatment had a higher trend in pCR. After excluding the Z1041 trial with high heterogeneity, the pCR of long-term treatment was significantly better than that of short-term treatment (RR =0.69, 95% CI: 0.50-0.95; P=0.02; I²=50%). The incidence of grade 3 and above adverse events in short-term treatment was significantly lower than that in long-term treatment (RR =0.75, 95% CI: 0.59-0.96; P=0.02; I²=0%). Subgroup analysis showed that in single anti-HER2 therapy, after excluding Z1041, the pCR of long-term treatment was better than that of short-term treatment (RR =0.61, 95% CI: 0.45-0.84; P=0.002; I²=0%); in the hormone receptor positive (HR+) group, after excluding Z1041, the pCR of long-term treatment was significantly better than that of shor-term treatment (RR =0.45, 95% CI: 0.24-0.83; P=0.01; I²=2%).

Conclusions: This meta-analysis indicates that when using single anti-HER2 therapy (trastuzumab + chemotherapy without additional anti-HER2 agents) for neoadjuvant treatment, a long-term treatment may bring better efficacy. In dual anti-HER2 therapy, the efficacy of long- and short-term treatments is similar, and a shorter treatment cycle can be considered to reduce adverse events.