Real-world prevalence of PD-L1 positivity in early-stage/metastatic triple-negative breast cancer: primary results and pathology insights from the global retrospective observational VANESSA study.

aimTo understand whether the worldwide implementation of PD-L1 testing in triple-negative breast cancer (TNBC) can be achieved in routine clinical practice. METHODS AND

resultsThe multicentre retrospective observational VANESSA study consecutively and uniformly enrolled patients treated with systemic therapy for early or metastatic (e/m)TNBC diagnosed between 2014 and 2017. PD-L1 status was retrospectively assessed locally and centrally using the VENTANA PD-L1 (SP142) Assay (PD-L1 expression on tumour-infiltrating immune cells covering ≥1% of the tumour area). The primary objective was to determine the prevalence of PD-L1 positivity assessed locally on primary and/or metastatic tumour tissue. Concordance between local and central testing was a secondary endpoint. PD-L1-positive prevalence was 38% in eTNBC (728/1902) and 20% in mTNBC (30/152) and was higher in submitted tissue size >5 versus <5 mm diameter (eTNBC: 43% versus 16%; mTNBC: 24% versus 13%). Among 1967 samples tested both centrally and locally, concordance was 75% (Cohen's κ coefficient 0.52, 95% CI 0.48-0.55) and was similar regardless of cohort (eTNBC versus mTNBC), sample collection method (biopsy versus resection) or sample origin (primary versus metastatic). PD-L1-positive prevalence was higher by central versus local assessment (eTNBC: 55% versus 39%; mTNBC: 26% versus 20%).

conclusionIn this real-world study, PD-L1-positive prevalence was lower than in prospective trials assessing PD-L1 status centrally, lower in mTNBC than eTNBC, lower in smaller than larger tissue samples and lower by local than central assessment. These findings underline the importance of central PD-L1 testing on sufficiently large samples to ensure optimal selection for therapies targeting PD-(L)1 in mTNBC.