Comparing the Efficacy of Various Treatment Strategies for Patients With Advanced Triple‐Negative Breast Cancer: An Umbrella Review

Chemotherapy (CT) remains the standard first-line treatment for advanced triple-negative breast cancer (aTNBC), despite the emergence of innovative therapies, including targeted therapies (TT) and immune checkpoint inhibitors (ICI). Studies have shown that the treatment strategies for aTNBC vary widely, with inconsistent efficacy across different treatment modalities. A comprehensive search was carried out in electronic databases, such as PubMed and Embase, for systematic reviews and randomized clinical trials (RCTs) that investigated the efficacy of TT, ICI, and CT to treat aTNBC until June 2025. Seventeen published meta-analyses and 52 RCTs reporting the prognosis of the disease treated with TT, ICI, and CT in aTNBC patients were analyzed. It showed that in terms of prolonging PFS, both the TT group and the ICI group were superior to the CT group [ICI: HR = 0.81 (0.69, 0.94); TT: HR = 0.68 (0.62, 0.74)]. In terms of OS, the TT group was superior to the CT group [HR = 0.77 (0.68, 0.88)]. In the subgroup analysis of TT, compared with CT alone, both sacituzumab govitecan (SG) monotherapy and trilaciclib combined with chemotherapy (TRI_CT) significantly improved the time of PFS [SG: HR = 0.41 (0.30, 0.56); TRI_CT: HR = 0.62 (0.46, 0.86)] and OS [SG: HR = 0.48 (0.33, 0.70); TRI_CT: HR = 0.41 (0.28, 0.59)]. This umbrella review supports SG monotherapy and TRI_CT as the first choice for patients with aTNBC. Additionally, the review was rated as high-quality evidence using AMSTAR 2, the credibility classification standard, and GRADE rating. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline and is registered with PROSPERO: CRD420251034666.