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

Purpose: Pembrolizumab 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.

Methods: A 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.

Results: Four 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.

Conclusion: Neoadjuvant 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.