Abstract 3225: A meta-analysis of single agent versus combination immune checkpoint inhibitors in metastatic triple negative breast cancer

Abstract Background: Immune checkpoint inhibitors (ICIs) are active against triple-negative breast cancer (TNBC), and approved in combination with chemotherapy, or as a single agent in patients with high tumor mutational burden and/or microsatellite instability/mismatch repair deficiency. A number of studies have been conducted with single-agent inhibitors of programmed cell death 1 or its ligand (PD1/PD-L1i), however, responses are typically low, especially in the later line setting. Few studies have evaluated the efficacy of PD1/PD-L1i combined with inhibitors of cytotoxic T-lymphocyte associated protein 4 (CTLA-4i) in metastatic TNBC, and none compared single agent vs combination ICI approaches. The purpose of this meta-analysis is to evaluate the efficacy of PD1/PD-L1i with or without CTLA-4i in TNBC. Methods: A comprehensive literature search across PubMed, Embase, and Cochrane Library identified 870 unique clinical trials from 2010 - 2024. Studies eligible for inclusion were those of patients with: (1) metastatic TNBC, (2) >1 line of prior therapy, (3) received PD1/PD-L1i with or without CTLA-4i. Studies of combination of ICI with chemotherapy or targeted treatments were excluded with the exception of histone-deacetylase inhibitor (HDACi) combinations. Data were selected and extracted by two reviewers based on the PRISMA-A guidelines. The primary objective of the meta-analysis was objective response rate (ORR). Progression-free (PFS) and overall survival (OS) were also determined when available. Results: A total of 10 clinical trials were eligible and included in the meta-analysis, six for single ICI and four for combination ICI. The heterogeneity test indicated no significant heterogeneity (I2) in either of the groups, thus, a fixed-effect model was used. A total of 611 patients with metastatic TNBC (>1L) treated with single ICI showed a pooled ORR of 8.3% (95% CI, 6.1-10.7%), median PFS of 1.7 months (95% CI 1.40-2.06) and OS of 9.13 months (95% CI, 8.09-10.17). Among 42 patients treated with combination ICI, a pooled ORR was 27.7% (95% CI, 14.1%-43.3%). A sensitivity analysis excluding patients that received an HDACi showed an ORR of 7.2% (95% CI, 4.4%-10.6%) vs. 24% (95% CI, 9.5%-41.6%) for the single and combination ICI groups, respectively. Conclusion: The use of combination ICI therapy led to an overall response rate of 27% compared to 8% in the single ICI studies. Our results provide rationale for further studies evaluating combination ICI approaches in patients with metastatic TNBC. Citation Format: Phaedon D. Zavras, Hugo R. Lara-Martinez, Qi Nie, Julius Y. Kattoula, Nicole Strossman, Zehui He, Ming Li, Romualdo Barroso-Sousa, Isaac Chan, Sara M. Tolaney, Vered Stearns, Cesar A. Santa-Maria, Evanthia T. Roussos Torres. A meta-analysis of single agent versus combination immune checkpoint inhibitors in metastatic triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3225.