A Meta-Analysis of Single Agent and Dual Immune Checkpoint Inhibitors in Metastatic Triple Negative Breast Cancer

Purpose : Single-agent programmed cell death-1 inhibitors or its ligand (PD-1/PD-L1i) demonstrate low response rates in metastatic triple-negative breast cancer (mTNBC), though a subset of patients may achieve durable responses. Data evaluating combined PD-1/PD-L1i and cytotoxic T-lymphocyte–associated protein 4 inhibition (CTLA-4i) are limited. We performed a meta-analysis evaluating the efficacy of single- and dual-agent immune checkpoint inhibitors (ICI) in mTNBC. Experimental Design : A comprehensive search of PubMed, Embase, and the Cochrane Library (2010–2024) identified 870 unique clinical trials. Eligible trials included patients with mTNBC who had received ≥1 prior line of therapy and were treated with PD-1/PD-L1i with or without CTLA-4i. Data were independently extracted by two investigators per PRISMA-A guidelines. The primary objective was objective response rate (ORR). Estimated progression-free survival (PFS) and overall survival (OS) at 6 and 12 months were also determined. Results : Ten trials were included; six single-agent and four dual-agent ICI. Among 728 patients treated with single-agent ICI, pooled ORR was 7.1% (95% CI, 5.3–9.2%), whereas, among 43 dual ICI recipients, pooled ORR was 29.4% (95% CI, 15.7–44.9%). Estimated 6- and 12-month PFS rates were 12.2%/5.5% for single ICI and 38.7%/31.4% for dual ICI. Estimated 12-month OS was 41.6% versus 56%, respectively. Among dual ICI recipients, 21% achieved disease control >12 months and 14% >24 months. Conclusions : Dual ICI therapy led to an ORR of 29% compared to 7% with single-agent ICI. Notably, a subset of patients can experience durable responses. These results provide a strong rationale for further studies evaluating combination ICI approaches in mTNBC.