Abstract 3783
Background
Evofosfamide (TH-302), a nitroimidazole-linked prodrug of a brominated version of isophosphoramide mustard, is converted to an activated form and acts as a DNA crosslinking agent when exposed to a hypoxic environment. Biliary tract cancer (BTC) is well known to contain large hypoxic area, and there is no standard 2nd line chemotherapy in advanced BTC. This study is a prospective, open-label, single-arm phase II trial to evaluate the efficacy and safety of evofosfamide as 2nd line treatment in advanced BTC.
Methods
Patients (pts) with unresectable or recurred BTC whose disease progressed after 1st line chemotherapy were enrolled. Pts received evofosfamide at a dose of 340 mg/m2 via intravenous (IV) infusion over 30 minutes on Day 1, 8, and 15 of every 28-day cycle. The primary end point was progression-free survival (PFS) rate at 4-months. Secondary end points included overall survival (OS), PFS, objective response rate (ORR), disease control rate (DCR), metabolic response by 18 F-FDG PET, and safety profile. Response evaluation was done every 8 weeks using RECIST v.1. Metabolic response was evaluated by PERCIST v.1, and toxicity was assessed by CTCAE v4.03.
Results
A total of 20 pts were treated with IP and 16 were response-evaluable. The median age was 58.7 years (range 54.90 - 62.29). The primary origin of tumor was intrahepatic cholangiocarcinoma in 9 pts, extrahepatic BTC 3, gallbladder cancer 6, and ampulla of vater 2. 16 pts had ECOG PS 0, and 4 had ECOG 1. There was no objective response, stable disease was observed in 9 pts, results in DCR 56.3%. The PFS rate at 4-months was 31.25%. The median PFS was 3.80 months (95% CI 1.03 - 6.57), and the median OS was 6.37 months (95% CI 3.94 - 8.79). Liver metastasis was associated with poor PFS. Reduction of tumor metabolic activity was observed in 8 pts out of 14 (57.1%). Majority of adverse events (AEs) were grade 1/2 ; neutropenia(30%), anemia (50%), thrombocytopenia (40%), nausea (15%), arthralgia (5%). Grade 3 anemia was observed in 15%, anorexia 5% and arthralgia 5%. There was no treatment-related death.
Conclusions
Evofosfamide monotherapy showed promising efficacy in terms of disease stabilization and PFS and OS, and acceptable AE profiles used as 2nd line treatment in advanced BTC.
Clinical trial identification
NCT02433639.
Legal entity responsible for the study
Do-Youn Oh, Seoul National University Hospital.
Funding
Merck Serono.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.