Abstract 48P
Background
We have already evaluated the feasibility (Phase Ib) and the potential benefits of regorafenib (Reg) in combination with chemotherapy in BTC (BREGO-NCT02386397).
Methods
BREGO is a multicenter phase II randomized trial. This trial will assess the safety and efficacy of m-GEMOX and Reg versus m-GEMOX alone. The stratification (2:1) of the 63 planned patients will be made according to the center and tumor localization (intra- versus extra-hepatic). Reg starting dose was 160mg daily from day 1 to day 14, with fixed doses of Gem (900 mg/m2) and Ox (80 mg/m2) on day 1 and 8 followed by 2 weeks’ rest.
Results
Sixty-three patients were randomised. Median age was 62.5 [31-75], male 56%, PS 0 (59%), 62% patients had intra hepatic CCK, 21% extra hepatic CCK and 17% gallbladder carcinoma. Median duration of Reg treatment was 5.1 months [0.46-19.32]; median number of mGEMOX cycles was 7 [2-17]. The median PFS was 7.82 months (95% CI: 5.78-8.15) in Reg-mGEMOX arm, and 7.23 months (95%CI: 7.58-11.2) in mGEMOX arm (p=0.825). The ORR/DCR were 33.3%/78% and 21.7%/82.6% in the Reg-mGEMOX and mGEMOX arms, respectively. The median OS was 13.5 months (95% CI: 9.69-16.76) in Reg-mGEMOX arm, and 15.08 months (95%CI: 8.8-NA) in mGEMOX arm (p=0.356). In subgroup analysis no differences were seen between intrahepatic or extrahepatic primary tumour location, but in experimental arm 25/42 patients continued Reg alone beyond 4 cycles (up to 28 cycles) experienced a strong improvement in term of DCR, PFS and OS. Main toxicities were (Reg-mGEMOX/mGEMOX) G3-4 neutropenia (16.7%/26.1%), G3-4 thrombocytopenia (23.8%/17.3%), G3 diarrhoea (4.8%/8.7%), G3 peripheral neuropathy (2.4%/4.3%), G3 HTA (7.1%/0%), and G2-3 hand-foot syndrome (16.7%/0%). Ancillary studies (PK, early metabolic response on PET scanner analysis and biomarkers (FGF19, SCT1) are ongoing to identify subpopulations of interest.
Conclusions
Even if the primary endpoint on PFS is not met in BREGO phase IIR trial, it proposes an alternative and probably a highly active regimen in a subgroup of metastatic or locally advanced biliary tract cancer patients. This new regimen is feasible and warrants biomarkers of response to further target patient who benefit of Reg combination.
Clinical trial identification
BREGO-NCT02386397
Editorial acknowledgement
Legal entity responsible for the study
ICM Montpellier, France.
Funding
Bayer Pharma company supported this project.
Disclosure
E. Assenat: Financial Interests, Personal, Advisory Board: Bayer; Roche; AstraZeneca; Ipsen; BMS; AAA; Sanofi. All other authors have declared no conflicts of interest.