Abstract PS5-03-23: Outcomes with first-line treatments for patients with locally advanced or metastatic triple negative breast cancer eligible for anti-PD-(L)1 therapy: A systematic literature review of randomized trials

Abstract Objective: To evaluate current treatment outcomes for patients with inoperable locally advanced or metastatic triple negative breast cancer (LA/mTNBC) whose tumors express programmed death-ligand 1 (PD-L1+) treated in the first line. Methods: Literature databases were searched to June 2024. Randomized trials involving adults with PD-L1+, (combined positive score [CPS] ≥1/immune cells ≥1% or receiving anti-PD-[L]1 therapy) inoperable LA/mTNBC treated in the first line were included. Results: From 4140 records, 50 reporting on eight phase 3, six phase 2 or 1/2 trials were included. The primary endpoint was progression-free survival (PFS) in 9 trials and overall survival (OS) in 5. Median PFS ranged from 3.6-12.2 months. Adding atezolizumab to taxane-based chemotherapies (7.2-7.5 vs. 5.3-6.4 months)—but not gemcitabine-carboplatin or capecitabine (4.2 vs. 3.6 months)—resulted in a significant PFS benefit. Adding pembrolizumab or toripalimab to standard chemotherapy also significantly improved PFS (9.7-10.8 vs. 5.6-6.7 months). There were also statistically significant improvements in PFS with molecular subtyping-based treatments and a numerical improvement in PFS when replacing nab-paclitaxel with sacituzumab govitecan (SG) combined with immunotherapy. Similarly, replacing chemotherapy with SG combined with pembrolizumab significantly increased PFS. Conversely, trials evaluating the addition of oleclumab, nivolumab, or ipatasertib to chemotherapy and/or immunotherapy did not significantly improve PFS. Median OS ranged from 10.7-32.8 months across trials; most showed no significant differences between treatment arms. However, adding atezolizumab (25.4 vs. 17.9 months) or toripalimab (32.8 vs. 19.5 months) to nab-paclitaxel significantly improved OS. Adding pembrolizumab to chemotherapy significantly improved OS only in patients with CPS ≥10 (23.0 vs. 16.1 months). Further trials investigating other immunotherapies added to standard chemotherapy did not significantly improve OS. Overall response rates (ORR) ranged from 23.1%-72.7%. All treatment arms, except nivolumab and toripalimab, resulted in a numerically higher ORR vs. comparator arms; however, statistical significance was rarely assessed and demonstrated only for the addition of atezolizumab to nab-paclitaxel. Overall, patients experiencing a serious adverse event ranged from 16%-44.4%. Conclusions: This review indicates an evolving treatment landscape, with the adoption of regimens with atezolizumab, toripalimab, pembrolizumab, and SG being associated with improved efficacy in patients with PD-(L)1-eligible LA/mTNBC. Specifically, the most recent publication revealed that SG in combination with pembrolizumab being a potential new frontline standard of care. Citation Format: X. Wang, J. Frampton, S. Pathak, M. Afshari, J. Dinoso, A. Brufsky. Outcomes with first-line treatments for patients with locally advanced or metastatic triple negative breast cancer eligible for anti-PD-(L)1 therapy: A systematic literature review of randomized trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-03-23.