Journal of gastrointestinal cancer · 2025
Combined Chemotherapy-Immunotherapy for Advanced Biliary Tract Cancer (BTC): A Clinical, Genomic, and Biomarker Analysis.
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Zhang Yong, Gou Miaomiao
Аннотация
BACKGROUND: Biliary tract cancer (BTC) represents a heterogeneous disease spectrum associated with an unfavorable prognosis. A combination of immunotherapy and chemotherapy has become a new standard strategy for advanced BTC. However, understanding the association between genomic alterations and outcomes of immunotherapy in BTC is crucial for further improving clinical benefits.
METHOD: Patients with metastatic BTC were included in this study retrospectively, who received PD-1/PD-L1 (ICI) antibodies combined with chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall response rate (ORR) and disease control rate (DCR). Additionally, we conducted exploratory analysis of genomic alterations and biomarkers.
RESULTS: Ninety-one patients were enrolled in this study. The patients were divided into two groups: albumin paclitaxel + S1 (AS) + PD-1 (n = 56) group and GC + ICI (n = 35) group. There were no significant differences in terms of PFS, ORR, and DCR between the two groups. Regarding biomarker analysis, 44 patients had positive PD-L1 expression, with a mPFS of 4.8 months and an ORR of 15.9%. Surprisingly, 29 patients had negative PD-L1 expression, with a mPFS of 9.9 months and an ORR of 27.6%. The average tumor mutational burden (TMB) was 4.5 mutations per megabase (mut/MB) for patients with microsatellite-stable (MSS) tumors. There was no significant difference in PFS between patients with TMB high and low (cutoff = 4.5 mut/MB). Genomic analysis revealed TP53 (n = 13, 43.3%), KRAS (n = 8, 26.7%), NTRK1/2/3 (n = 8, 26.7%), isocitrate dehydrogenase (IDH) 1/2 (n = 6, 20.0%), PIK3CA (n = 6, 20.0%), BRCA2 (n = 5, 16.7%), MDM2/4 (n = 5, 16.7%), and BRAF (n = 4, 13.3%) as the most common gene alterations. MDM2/4 mutations were associated with shorter survival (p < 0.05).
CONCLUSION: GC plus immunotherapy is still the standard of care for late stage BTC. PD-L1 expression and TMB were not good predictors for selecting patients who would benefit more from immunotherapy plus chemotherapy.
METHOD: Patients with metastatic BTC were included in this study retrospectively, who received PD-1/PD-L1 (ICI) antibodies combined with chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall response rate (ORR) and disease control rate (DCR). Additionally, we conducted exploratory analysis of genomic alterations and biomarkers.
RESULTS: Ninety-one patients were enrolled in this study. The patients were divided into two groups: albumin paclitaxel + S1 (AS) + PD-1 (n = 56) group and GC + ICI (n = 35) group. There were no significant differences in terms of PFS, ORR, and DCR between the two groups. Regarding biomarker analysis, 44 patients had positive PD-L1 expression, with a mPFS of 4.8 months and an ORR of 15.9%. Surprisingly, 29 patients had negative PD-L1 expression, with a mPFS of 9.9 months and an ORR of 27.6%. The average tumor mutational burden (TMB) was 4.5 mutations per megabase (mut/MB) for patients with microsatellite-stable (MSS) tumors. There was no significant difference in PFS between patients with TMB high and low (cutoff = 4.5 mut/MB). Genomic analysis revealed TP53 (n = 13, 43.3%), KRAS (n = 8, 26.7%), NTRK1/2/3 (n = 8, 26.7%), isocitrate dehydrogenase (IDH) 1/2 (n = 6, 20.0%), PIK3CA (n = 6, 20.0%), BRCA2 (n = 5, 16.7%), MDM2/4 (n = 5, 16.7%), and BRAF (n = 4, 13.3%) as the most common gene alterations. MDM2/4 mutations were associated with shorter survival (p < 0.05).
CONCLUSION: GC plus immunotherapy is still the standard of care for late stage BTC. PD-L1 expression and TMB were not good predictors for selecting patients who would benefit more from immunotherapy plus chemotherapy.