UK ABC-02 trial: Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial. Authors: Juan Valle et al Reviewed by : Scott Berry Date posted: June 2009

Cisplatin 25 mg/m2 + Gem 1000 mg/m2 D1,8,15 q 28d 24 weeks (6 cycles) N=410 R Cisplatin 25 mg/m2 + Gem 1000 mg/m2 D1,8 q 21d 24 weeks (8 cycles) Locally Advanced/ Metastatic CholangioCA Gall Bladder CA Periampullary CA

RESULTS Gem Gem/Cis 16% 26% p=0.25 6.5 8.4 P=0.003 8.3 11.7 P=0.002 p-value Response Rate (%) 16% 26% p=0.25 PFS (median, mos) 6.5 8.4 P=0.003 OS (median, mos) 8.3 11.7 P=0.002

Adverse events: Grade 3-4  Toxicity by patient Gem Cis/Gem   % White blood cells 11.0% 15.1% Platelets 8.0% 8.2% Haemoglobin 3.7% 6.3% Neutrophils 17.9% 22.6% Infection + neutropaenia 7.5% 10.2% Infection - neutropaenia 8.6% 6.4% Bilirubin 13.1% 10.7% ALT 18.1% 9.6% AST 11.4%

Adverse events: Grade 3-4 Toxicity by patient Gem (n, %) Cis/Gem (n, %) Anorexia 2.5% 1.9% Lethargy 16.6% 18.6% Nausea 3.1% 3.2% Renal function 1.2% Vomiting 3.0% 5.1% Constipation 1.8% 1.3% Diarrhoea 4.5% Dyspnoea Pedal oedema 2.6% Pain 7.5% 9.0% Any grade ≥3 events 65.5% 64.2%

STUDY COMMENTARY First demonstration of survival benefit in advanced biliary cancer Statistically and Clinically significant improvement Benefit gained with no clinically significant added toxicity

BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS Important trial that demonstrated a clinically significant survival benefit with an inexpensive and easily available agent The control arm of NCIC BI.1 (Gem vs Gem / Capecitabine) will need to be re-considered given the results of this trial