SynthesisSystematic reviews2026
Efficacy of dual HER2 blockade in neoadjuvant HER2-positive breast cancer: a meta-analysis of RCTs.
Synthesis in Systematic reviews, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionHER2-positive breast cancer is an aggressive subtype that benefits from targeted therapies. According to the Chinese Society of Clinical Oncology (CSCO) guidelines and the National Comprehensive Cancer Network (NCCN), the combination of trastuzumab (H) with pertuzumab (P) and neoadjuvant chemotherapy has become the standard treatment for patients with HER2-positive breast cancer in the neoadjuvant setting. Nevertheless, the long-term survival benefits of neoadjuvant dual HER2 blockade (P + H) remain unaddressed by comprehensive meta-analyses to date. This study is the first systematic review and meta-analysis to directly compare the long-term efficacy of P + H vs. H (excluding trastuzumab-derived or similar drugs, such as T-DM1, T-DXd, and so on) in the neoadjuvant treatment of HER2-positive breast cancer.
methodsWe conducted a systematic literature search in PubMed, Embase, the Cochrane Library, CNKI, Wan Fang, and VIP databases for relevant studies published up to June 1, 2025. RCTs with HER2-positive breast cancer patients who had not received breast cancer-related treatments previously were included. Treatment of P + H or H arms with chemotherapy combined with pertuzumab plus trastuzumab or trastuzumab as neoadjuvant treatment. The primary outcome was the event-free survival (EFS), disease-free survival (DFS), and overall survival (OS), and secondary outcomes included total pathological complete response (tpCR), objective response rate (ORR), and grade ≥ 3 adverse effects (AEs). The quality of evidence was assessed using the GRADE.
resultsA total of six RCTs involving 803 patients were included. In long-term efficacy, the P + H arm showed significant improvements in 3-year EFS rate (RR 1.08, 95% CI 1.00-1.16, p = 0.04), 5-year EFS rate (RR 1.10, 95% CI 1.01-1.20, p = 0.03), 5-year EFS (HR 0.58, 95% CI 0.38-0.87, p = 0.009), 5-year DFS rate (RR 1.09, 95% CI 0.99-1.20), and 5-year DFS (HR 0.55, 95% CI 0.35-0.84), compared to the H arm. In short-term efficacy, the P + H arm showed significant improvements in tpCR (RR 1.76, 95% CI 1.39-2.23, p < 0.001) and ORR (RR 1.18, 95% CI 1.09-1.27, p < 0.001) compared to the H arm. The outcome of 5-year DFS rate had moderate-quality evidence, and the outcome of 3-year EFS rate, 5-year EFS rate, 5-year EFS (HR), 5-year DFS (HR), tpCR had high-quality evidence.
conclusionsDual HER2 blockade with pertuzumab and trastuzumab demonstrated superior short- and long-term efficacy compared with trastuzumab alone, with each treatment showing a distinct but manageable safety profile. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021286130.
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