Association of PD-L1 combined positive score with disease control and response kinetics with first-line pembrolizumab-based therapy in metastatic triple-negative breast cancer: results from routine clinical practice in Poland

Programmed death-ligand 1 (PD-L1) expression assessed by the combined positive score (CPS) is required for eligibility to first-line pembrolizumab-based therapy in metastatic triple-negative breast cancer (mTNBC). However, the predictive value of CPS beyond treatment eligibility, particularly for disease control, response kinetics and response durability in real-world practice, remains uncertain. This study evaluated the association between CPS analyzed as a continuous variable and clinical outcomes in a Polish real-world mTNBC population.

This multicenter retrospective study included patients with PD-L1-positive (CPS ≥ 10) mTNBC treated with first-line pembrolizumab plus chemotherapy across 13 oncology centers in Poland (2022–2025). CPS was assessed locally and primarily analyzed as a continuous variable with exploratory categorical analyses performed for descriptive and visualization purposes. Primary endpoints included objective response rate (ORR), disease control rate (DCR), and progression as best response. Secondary endpoints were time to best response (TTBR) and duration of response (DoR).

Seventy-two patients were eligible for analysis. Median age was 57 years (IQR 48–67) and median CPS was 20 (IQR 15–50). After a median follow-up of 11.6 months, ORR was 48.6% and DCR was 88.9%. CPS did not differ between patients achieving ORR versus no ORR (p = 0.58) or DCR versus no DCR (p = 0.56), nor was it associated with progression as best response. CPS showed no correlation with TTBR (ρ = 0.02, p = 0.9) or DoR (ρ = –0.33, p = 0.05). In univariable analysis, CPS was not associated with PFS. However, in multivariable Cox regression, CPS showed a statistically significant association with PFS, although the effect size was minimal (HR 1.01 per CPS unit).

In real-world PD-L1-positive mTNBC, CPS was not significantly associated with response outcomes. Although statistically linked to PFS, the effect was minimal and likely not clinically meaningful, supporting its role as a threshold-based rather than quantitative biomarker.