Liver international : official journal of the International Association for the Study of the Liver · 2025
Sunitinib as Second-Line Treatment in Advanced Intrahepatic Cholangiocarcinoma: Results From the SUN-CK GERCOR Phase II Trial.
СтатьяКлиническое исследование II фазыМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gros Louis, Bouattour Mohamed, Dumont Clément, Dahan Laëtitia, Malka David, Tijeras-Raballand Annemilaï, De Gramont Armand, Ronot Maxime, Dreyer Chantal, Neuzillet Cindy, Bourget Philippe, Hadengue Alexandra, Roldan Nelly, Garcia-Larnicol Marie-Line, Chibaudel Benoist, Raymond Eric, Faivre Sandrine
Аннотация
BACKGROUND & AIMS: Angiogenesis is critical in intrahepatic cholangiocarcinoma (ICC), a highly lethal cancer with limited treatment options. Sunitinib, a multi-receptor tyrosine kinase inhibitor, has strong antiangiogenic and antitumor effects. We aimed to evaluate the efficacy and tolerability of sunitinib as a second-line treatment in chemotherapy-pretreated patients with advanced ICC.
METHODS: This open-label, single-arm, phase II trial was conducted across five French centres. Eligible patients were aged ≥ 18, had advanced ICC not suitable for curative surgery and had been pre-treated with gemcitabine and/or platinum. Patients received oral sunitinib at 37.5 mg daily. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Tumour response was evaluated using RECIST v1.1, with exploratory analysis using Choi criteria. VEGF-A, VEGF-C and plasma sunitinib levels were measured.
RESULTS: Fifty-three patients were included. Median OS was 9.6 months (95% CI, 6.1-13.1), median PFS was 3.7 months (95% CI, 3.1-6.4), the ORR was 14% and the DCR was 84%. Grade 3-4 cytopenias occurred in 25% of patients, hypertension in 21% and fatigue in 19%. Higher baseline levels of VEGF-A and VEGF-C correlated with longer OS. Patients with dose reductions maintained adequate drug exposure. Choi criteria, applied to 24 patients, predicted response duration better than RECIST v1.1. Baseline tumour density, assessed in 14 patients, showed a potential association with treatment responses.
CONCLUSIONS: Sunitinib demonstrated efficacy and manageable toxicity as a second-line treatment in patients with advanced ICC previously treated with chemotherapy, suggesting it may represent a viable therapeutic option for this population.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01718327.
METHODS: This open-label, single-arm, phase II trial was conducted across five French centres. Eligible patients were aged ≥ 18, had advanced ICC not suitable for curative surgery and had been pre-treated with gemcitabine and/or platinum. Patients received oral sunitinib at 37.5 mg daily. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Tumour response was evaluated using RECIST v1.1, with exploratory analysis using Choi criteria. VEGF-A, VEGF-C and plasma sunitinib levels were measured.
RESULTS: Fifty-three patients were included. Median OS was 9.6 months (95% CI, 6.1-13.1), median PFS was 3.7 months (95% CI, 3.1-6.4), the ORR was 14% and the DCR was 84%. Grade 3-4 cytopenias occurred in 25% of patients, hypertension in 21% and fatigue in 19%. Higher baseline levels of VEGF-A and VEGF-C correlated with longer OS. Patients with dose reductions maintained adequate drug exposure. Choi criteria, applied to 24 patients, predicted response duration better than RECIST v1.1. Baseline tumour density, assessed in 14 patients, showed a potential association with treatment responses.
CONCLUSIONS: Sunitinib demonstrated efficacy and manageable toxicity as a second-line treatment in patients with advanced ICC previously treated with chemotherapy, suggesting it may represent a viable therapeutic option for this population.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01718327.