Neoadjuvant dose-dense anthracycline and cyclophosphamide in combination with carboplatin, paclitaxel, and pembrolizumab for triple-negative breast cancer: a systematic review and meta-analysis

PurposePembrolizumab in combination with chemotherapy has become the standard neoadjuvant regimen for triple-negative breast cancer (TNBC). However, the KEYNOTE-522 trial did not use dose-dense (dd) anthracycline and cyclophosphamide (AC) as part of its chemotherapy backbone. This meta-analysis assesses the efficacy and safety of neoadjuvant ddAC in combination with carboplatin and paclitaxel (CT) and pembrolizumab.MethodsA systematic search was conducted to identify studies evaluating neoadjuvant ddAC in combination with CT and pembrolizumab, with or without comparisons to 3-weekly AC in TNBC. Statistical analysis was performed using random-effects model for studies comparing two schedules, and single-arm proportional meta-analysis to summarize endpoints for dose-dense regimen.ResultsFour observational studies, comprising 535 patients (329 receiving ddAC and 206 receiving 3-weekly AC), met the inclusion criteria. Three studies compared the two schedules, while one evaluated ddAC. No difference in pCR was observed between both schedules (66.1% vs. 61.6%; RR 1.10; 95% CI 0.94-1.28; p = 0.25). However, patients receiving ddAC experienced higher incidence of grade III-IV adverse events (43.7% vs. 29.7%; RR 1.65; 95% CI 1.15-2.37; p = 0.007). No differences were found in dose modifications or treatment delays between the two schedules. In the combined analysis of studies evaluating ddAC, the overall pCR was 63%, with a 40% incidence of treatment delays. No included studies reported survival data for ddAC patients.ConclusionNeoadjuvant pembrolizumab with ddAC demonstrated a pCR incidence comparable to that reported in the KEYNOTE-522 trial. When compared to 3-weekly AC, ddAC was associated with a higher toxicity, with no difference in pCR.