A Santoro1, V Gebbia2, T Pressiani3, A Testa2, N Personeni3, E Arrivas Bajardi2, P Foa4, A Buonadonna5, K Bencardino6, C Barone7, D Ferrari4, A Zaniboni8, M C Tronconi3, G Cartenì9, M Milella10, A Comandone11, S Ferrari12, L Rimassa3. 1. Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan armando.santoro@cancercenter.humanitas.it. 2. Department of Medical Oncology, Nursing Home 'La Maddalena', Palermo. 3. Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan. 4. Department of Medical Oncology, 'San Paolo' University Hospital, Milan. 5. Oncology Referral Center, IRCCS, Aviano. 6. Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan. 7. Department of Medical Oncology, Università Cattolica del S. Cuore, Rome. 8. Department of Oncology, 'Poliambulanza' Foundation, Brescia. 9. Department of Oncology, Cardarelli Hospital, Naples. 10. Medical Oncology A, Regina Elena National Cancer Institute, Rome. 11. Department of Oncology, Gradenigo Hospital, Turin. 12. Oncology Unit, AstraZeneca, Basiglio, Italy.
Abstract
BACKGROUND: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. PATIENTS AND METHODS: Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. RESULTS: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). CONCLUSIONS: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. CLINICAL TRIAL NUMBER: NCT00753675.
BACKGROUND: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. PATIENTS AND METHODS: Patients were randomized in a 1 : 1 : 1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m(2) was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. RESULTS: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). CONCLUSIONS: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. CLINICAL TRIAL NUMBER: NCT00753675.
Authors: Avani Athauda; Caroline Fong; David K Lau; Milind Javle; Ghassan K Abou-Alfa; Chigusa Morizane; Keith Steward; Ian Chau Journal: Cancer Treat Rev Date: 2020-03-12 Impact factor: 12.111