Key points are not available for this paper at this time.
Introduction Immunotherapy recently approved with first-line (1L) chemotherapy for advanced biliary tract cancer (aBTC). Translational research is warranted to identify biomarkers for efficacy. Methods This prospective multicenter non-randomised phase-II study recruited 50 treatment-naïve proven aBTC patients for cisplatin and gemcitabine with pembrolizumab until disease progression or unacceptable toxicity. Primary endpoint was progression-free survival at 6 months (6mPFS, RECIST v.1.1). Secondary endpoints were overall survival (OS), radiological responses and safety. Exploratory translational research was to identify predictive biomarkers. Tumour tissue and blood were collected for MMR, PD-1/PD-L1 in T-cells, monocytes and myeloid derived suppressor cells (MDSCs). Results Fifty patients were 38% male, aged 63 (35–84) years. 6mPFS was 61.2% (80% CI 51.7–69.5) with mPFS 8.3 months (95% CI 5.6–10.6); ORR 40.8% (95% CI 27.0–55.8). Med. OS was 13.4 months (95% CI 8.3–20.5) with 24-months-OS 28.4% (95% CI 16.6–41.4). Higher PD-L1 expression correlated with improved PFS (HR=0.59; 95% CI: 0.26–1.37) and OS (HR=0.68; 95% CI: 0.28–1.64). Responders showed higher CD8/Treg ratio than non-responders (26.2% vs 21.2%) and lower CD4/PD1+ and CD8/PD1+ T-cells (33.5% vs 41.5% and 26.4% vs 44.7%) respectively. During treatment, profiling decreased in CD4/PD1+ and CD8/PD1+ Tcells (36.0% vs 22.2% and 41.6% vs 21.0%) respectively. MDSCs increased in non-responders. Responders, CPS-positive and low-stage patients showed normal Neutrophil-Lymphocyte-Ratios. Conclusion Pembrolizumab plus CisGem showed consistent efficacy to prior phase-III trials. Biomarkers suggest baseline immune landscape influences responses, T-cell exhaustion and immunosuppressive myeloid expansion. Immune phenotyping supports patient selection and further biomarker-driven trials in BTC.
Lamarca et al. (2026) studied this question.