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Safety and efficacy of GEMOX plus donafenib and tislelizumab as first-line therapy for advanced epithelial malignant biliary tract cancer
Background
Nearly 70% of the newly diagnosed patients with malignant biliary tract cancer (BTC) are in advanced stage. Gemcitabine-based systemic chemotherapy is the standard first-line treatment. Chemotherapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors as the first-line treatment has shown good efficacy but the safety profile remains to be improved. The purpose of this study was to evaluate the safety and efficacy of gemcitabine and oxaliplatin (Gemox) plus donafenib and tislelizumab.
Methods
In this prospective single-center exploratory study, eligible patients were aged 18–80 years (inclusive) with histologically or cytologically documented stage III/IV (AJCC Cancer Staging Manual, 8th Edition) epithelial malignant biliary tract cancer, at least one measurable disease per RECIST v1.1, ECOG performance status (PS) of 0–1, main organs function well and life expectancy of at least three months. Patients received gemcitabine 1000 mg/m2 IV Q3W, oxaliplatin 100 mg/m2 IV Q3W, donafenib 200 mg PO BID and tislelizumab 200 mg IV Q3W until disease progression, unacceptable toxicity or withdrawal of consent whichever occurred first. The primary endpoint was safety. The secondary endpoints included conversion rate and overall survival (OS).
Results
From March 2021 to August 2021, 13 patients were enrolled (5 males and 8 females; 4 stage III and 9 stage IV; all ECOG PS of 1; aged 53–72 years; 4 gallbladder cancer, 2 hilar cholangiocarcinoma and 7 intrahepatic cholangiocarcinoma). The median (IQR) levels of CA-199, AFP and CEA at baseline were 125 U/ml (4.5–1000), 3.5 ng/ml (1.8–11.4) and 6.3 ng/ml (1.6–12.8), respectively. At data cut-off (February 17, 2022), a median number of 4 cycles (range 1–14) of study treatment was received and the median treatment duration of donafenib was 87 days (range 17–277). The median follow-up time was 147 days (range 18–277). Treatment-related adverse events (TRAEs) occurred among all patients (100%), including 7 (53.8%) patients who had grade 3 TRAEs and one (7.7%) patient who had a grade 4 TRAE. No grade 5 TRAE or unexpected adverse event was reported. The most frequently reported grade 3-4 TRAEs were rash (4/13, 30.8%), platelet count decreased (2/13, 15.4%) and fatigue (2/13, 15.4%). Three stage III patients underwent subsequent surgery with a conversion rate of 23.1% (95% CI, 5.0%–53.8%). The median OS was not reached. The 6-month OS rate was 90.9% (95% CI, 50.8%–98.7%).
Conclusions
GEMOX plus donafenib and tislelizumab as the first-line therapy for advanced BTC showed manageable toxicity and encouraging efficacy especially in terms of a promising conversion rate in stage III patients.
Clinical trial identification
NCT04979663.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
