Homologous recombination deficiency (HRD) is a key molecular feature in a subset of triple-negative breast cancer (TNBC). The optimal treatment strategy for metastatic TNBC with HRD remains unclear despite multiple therapeutic options.

A systematic search was performed in PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov, including conference proceedings, up to November 27, 2024. Eligible studies included randomized controlled trials and retrospective studies reporting efficacy outcomes for metastatic TNBC with HRD biomarkers. Pairwise meta-analysis using random-effects models and Bayesian network meta-analysis were conducted. Hazard ratios (HRs) or odds ratios (ORs) with 95% credible intervals (CrIs) were used. Primary outcomes included progression-free survival (PFS) and overall survival (OS); secondary outcomes were objective response rate (ORR) and adverse events (AEs). Treatment rankings were estimated using the surface under the cumulative ranking curve (SUCRA).

Thirteen studies with 1,341 patients and 8 treatment regimens were included. For metastatic TNBC with HRD, PARP inhibitors (PARPi), platinum-based chemotherapy (PBCT), and PARPi + PBCT significantly improved PFS compared to platinum-free chemotherapy (PFCT) (HR 0.53, 95% CrI 0.31–0.90; HR 0.60, 95% CrI 0.35–0.90; HR 0.41, 95% CrI 0.20–0.74). PARPi + PBCT ranked highest for PFS (SUCRA = 78.8%), while sacituzumab govitecan (SG) ranked highest for OS (SUCRA = 86.1%). PARPi + ATR inhibitor (ATRi) showed the highest ORR (SUCRA = 75.8%). PARPi + PBCT had the highest all-grade AEs (SUCRA = 30.5%), with PFCT having the lowest (SUCRA = 77.6%). In addition, SG was associated with the highest incidence of grade ≥ 3 AEs (SUCRA = 11.0%).

PARPi + PBCT was associated with the most favorable PFS, whereas SG ranked highest for OS in patients with metastatic TNBC with HRD. These findings highlight distinct advantages across efficacy endpoints and underscore the need to balance efficacy and safety when selecting treatment strategies.