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A randomized, double-blind, multicenter phase II AIO trial with gemcitabine plus sorafenib versus gemcitabine plus placebo in patients with chemotherapy-naive advanced or metastatic biliary tract cancer: First safety and efficacy data.

4077 Background: Despite recent progress in chemotherapy (Valle, 2010), new therapy options are urgently needed for advanced or metastatic biliary tract cancer (mBTC). The objectives of this randomized, double-blind, multicenter phase II trial were safety and clinical activity of gemcitabine (GEM) combined with sorafenib versus placebo (Sor/Pl) as first-line therapy in mBTC.


METHODS
GEM (1,000 mg/m²) was given on day 1, 8, 15, 22, 29, 36, 43 in first cycle and day 1, 8, 15 of all other cycles. Sor/Pl tablets were administered as a dose of 400 mg bid orally. Preliminary incomplete data of 103 full recruited, but still blinded patients could be analysed. Since patients are still under treatment, data are shown for both groups together.


RESULTS
Out of 62 patients, 9/40/13 had gallbladder, intrahepatic or hepatic BTC, respectively. Median age was 64.5 years (range 36-93). Median size of target lesions was 80 mm (range 10-271). Median time after diagnosis was 25 days (range 1-2633). Reasons for treatment end of 47 patients were PD (27) death (7) deterioration (6) or other reasons (7). Most patients had > 1 cycle. Duration of GEM and Sor/Pl was 64 (range 1-330) and 66 days (range 8-375), respectively. 106 adverse events of 69 patients (67%) were expected as known study medication toxicities. Most frequent SAEs (grade 1-3) were health deterioration 16%, abdominal pain 12%, cholangitis 12%, pyrexia 12% and nausea 7%. In 25%, SAE outcome was death, none assessed related to sorafenib. Out of 8 SUSARs, 3 were possibly related to Sor (blurred vision; atrial fibrillation; respiratory infection) . Response were available for 46 patients. PR and SD was 7% and 63% patients, respectively. Disease control rate was 70%. Median PFS and OS calculated for 73 patients was 86 (95% CI: 67-148), and 281 days (95% CI: 160-342), respectively, with 51% for PFS and 36% for OS.


CONCLUSIONS
The preliminary activity and manageable toxicity data suggest that gemcitabine combined with sorafenib/placebo can be an option as first-line therapy of advanced BTC. The role of sorafenib combined with chemotherapy warrants further investigation.