Systematic review and meta-analysis of PD-1 and PD-L1 inhibitors in triple-negative breast cancer: A focus on survival, metastasis, and recurrence.
Year: 2025
Type: conference-abstract
Abstract: e13140 Background: Triple-negative breast cancer (TNBC) is an aggressive and highly heterogeneous subtype of breast cancer. It accounts for 10–15% of all breast cancer cases and is associated with a poor prognosis, with a 5-year mortality rate of approximately 40%. Due to its immunogenic profile, marked by high PD-L1 expression and increased tumor-infiltrating lymphocytes, immune checkpoint inhibitors (ICIs), particularly PD-1 and PD-L1 inhibitors, have shown promise in the neoadjuvant and metastatic settings. Despite these advancements, the impact of ICIs on survival, recurrence, and metastasis remains inconsistent, necessitating further exploration. Methods: A systematic review and meta-analysis adhering to PRISMA guidelines was conducted to evaluate the efficacy and safety of PD-1 and PD-L1 inhibitors in metastatic TNBC. Randomized controlled trials (RCTs) and observational studies published through June 2024 were included. Out of 984 articles screened, 10 met the inclusion criteria, a total of 5,945 participants treated with either a PD-1 or PD-L1 inhibitor. The primary outcomes assessed were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Statistical heterogeneity was assessed using I², and sensitivity analyses were performed to address outliers. Subgroup analyses evaluated the efficacy of ICIs based on PD-L1 expression levels and treatment regimens. Results: A total of 10 studies comprising 5,973 patients were included. The pooled HR for PFS was 0.93 (95% CI: 0.64-1.37, p = 0.73, I 2 = 92.1%) with no statistically significant effect; however, sensitivity analysis excluding an outlier study showed a significant improvement in PFS (HR: 0.81, 95% CI: 0.72-0.92, p = 0.001, I² = 0%). For OS, the pooled HR was 0.96 (95% CI: 0.84-1.09, p = 0.50, I² = 35.1%). Subgroup analyses revealed enhanced efficacy in PD-L1-positive patients, with higher response rates and survival benefits. Adverse events (AEs) of grade 3 or higher occurred at a similar rate in treated patients (OR: 1.09, 95% CI: 0.64-1.87, p = 0.74, I² = 90.3%), with atezolizumab showing a higher incidence of treatment-related toxicities compared to pembrolizumab. Conclusions: PD-1 and PD-L1 inhibitors demonstrate promising efficacy in improving pathological complete response rates and survival outcomes in PD-L1-positive TNBC patients, particularly in the neoadjuvant and metastatic settings. However, high heterogeneity in study results and limited benefit in unselected populations underscore the need for further refinement in patient selection and biomarker development. Immune-related adverse events remain a concern and warrant careful monitoring. Future clinical trials should focus on optimizing treatment combinations and understanding mechanisms of resistance to maximize the therapeutic potential of ICIs in TNBC.
Source: Journal of Clinical Oncology
Authors: Milton Abraham Trujillo Asturias, Jose Ramon Flores Valdes, Rafael Pinto-Colmenarez, Omar A Borges-Sosa, Jaqueline Livier Castillo, Marian Vianey Iniesta Vallejo, Angel Ayala, Mauricio Montelongo-Quevedo, Nitzia Esmeralda Quilantan, Ana Maria Mendoza Sanchez, Julieta Arguelles-Hernandez, Luis Norzagaray Figueroa, Jennifer Castillo, Julio Antonio Peguero
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410804535