Survival benefit and safety profile of PD-1/PD-L1 inhibitors in advanced triple-negative breast cancer: A systematic review and meta-analysis

This project is a systematic review and meta-analysis designed to evaluate the survival benefit and safety profile of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors in adults with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Although immune checkpoint inhibitors have emerged as an important therapeutic option in advanced TNBC, randomized trials have reported heterogeneous results influenced by differences in PD-L1 biomarker assessment, chemotherapy backbones, geographic populations, and line of therapy. The primary objective of this review is to quantify the pooled effects of PD-1/PD-L1 inhibitor–based regimens on overall survival (OS) and progression-free survival (PFS) compared with non-immunotherapy control regimens. Secondary objectives include evaluation of objective response rate (ORR) and the incidence of treatment-related, serious, and immune-related adverse events. Prespecified subgroup analyses will explore effect modification by PD-L1 expression status, line of therapy, checkpoint inhibitor class, and chemotherapy partner. Eligible studies include phase II–III randomized controlled trials enrolling adult patients with advanced TNBC. Random-effects meta-analytic models with Hartung–Knapp adjustment will be used to synthesize hazard ratios and risk ratios. Risk of bias will be assessed using the Cochrane RoB 2 tool, and certainty of evidence will be evaluated using the GRADE framework. This registration aims to enhance methodological transparency, minimize selective reporting, and provide a predefined analytical plan prior to data synthesis. Findings are expected to clarify the magnitude and consistency of survival benefit and inform biomarker-guided clinical decision-making in advanced TNBC.