Abstract
<title>Abstract</title> <p>Purpose Trastuzumab and pertuzumab plus a taxane is a standard neoadjuvant regimen for HER2-positive breast cancer; adding carboplatin (TCbHP) increases hematologic toxicity. We evaluated whether carboplatin-free regimens (THP) preserve efficacy while reducing toxicity. Methods We searched PubMed, Embase, and Cochrane CENTRAL through 15 June 2025, plus major oncology conferences, for randomized and non-randomized studies comparing six cycles of neoadjuvant THP versus TCbHP in stage II-III HER2-positive breast cancer (PROSPERO CRD420251084035). The primary outcome was pathologic complete response (pCR); secondary outcomes were grade 3–4 hematologic toxicity and tolerability. Risk ratios (RRs) were pooled with DerSimonian-Laird random-effects models; certainty of evidence was rated with GRADE. Results Seven studies (2,061 patients; 989 THP, 1,072 TCbHP) were included. The pooled pCR rate was 61.9% (THP) versus 63.9% (TCbHP) (RR 0.92, 95% CI 0.79–1.07; I²=69%); this heterogeneity was driven by study design, with neutral efficacy in randomized trials (RR 1.06) and a TCbHP advantage in observational studies (RR 0.80). THP reduced grade 3–4 hematologic toxicity: neutropenia RR 0.45 (95% CI 0.32–0.63), thrombocytopenia RR 0.09 (0.03–0.29), and anemia RR 0.35 (0.18–0.67), all with low heterogeneity (I²≤16%). Conclusion THP did not meet an exploratory, post hoc non-inferiority benchmark for pCR, but the small efficacy difference combined with a consistently superior hematologic safety profile supports carboplatin-free therapy as a reasonable de-escalation option for selected patients at high risk of hematologic toxicity.</p>