A Single-Arm Phase II Study of Nab-Paclitaxel Plus Gemcitabine and Cisplatin for Locally Advanced or Metastatic Biliary Tract Cancer

Abstract

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients.

Materials and methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy.

Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients' survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1-positive (PD-1+) cells (p=0.032) were observed in the response patients.

Conclusion: In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Keywords: Biliary tract neoplasms; Cisplatin; Gemcitabine; Nab-paclitaxel; Tumor microenvironment.

Fig. 1.

Patient enrollment and disposition. AEs, adverse events; GAC, nab-paclitaxel plus gemcitabine and cisplatin; OS, overall survival; PFS, progression-free survival.

Fig. 2.

Efficacy data from whole populations. (A) Progression-free survival of all treated patients. (B) Overall survival of all treated patients. (C) Best response of tumor lesions. (C) Best response of tumor lesions. (D) Change of tumor diameters. (E) Treatment features of whole populations. CI, confidence interval; mOS, median overall survival; mPFS, median progression-free survival.

Fig. 3.

Kaplan-Meier curves based on tumor markers. (A) Carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) baseline and post-treatment levels and their post-treatment changes in relation to progression-free survival. (B) Baseline and post-treatment levels of CA19-9 and CEA and their post-treatment changes in relation to overall survival.

Fig. 4.

Multiplex immunofluorescence analysis of tumor microenvironment (TME) before treatment. (A) Representative fluorescence images of a response patient illustrating the higher number of CD4+, CD8+ T-cell infiltrate before treatment. (B) Representative fluorescence images of a non-response patient illustrating the lower number of CD4+, CD8+ T-cell infiltrate and higher number of programmed death-1–positive (PD-1+), TIGIT+ T-cell infiltrate before treatment. (C-G) Comparison of different types of immune cells in the TME of response and non-response patients. ^*p < 0.05, ^**p < 0.01; ns, not significant.