SUMMARY: Bile Duct cancer (Cholangiocarcinoma), comprise about 30% of all primary liver tumors and includes both intrahepatic and extrahepatic bile duct cancers. About 8,000 people in the US are diagnosed with bile duct cancer each year. The average age of an individual in the US diagnosed with bile duct cancer is 71 years and approximately 20% of the cases are suitable for surgical resection. The 5-year survival is less than 10%. There is no standard adjuvant therapy for patients with resectable bile duct cancer, although adjuvant intervention in a previously reported meta-analysis showed improved Overall Survival (Horgan AM, Amir E, Walter T, et al. JCO 2012;30:1934-1940).
The BILCAP trial is a phase III study conducted to determine whether XELODA® (Capecitabine) improved Overall Survival (OS) compared to Observation, following radical surgery. In this trial, 447 patients were randomized to receive XELODA® (N=223) or Observation (N=224). Eligible patients had completely resected, cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate), with a R0 resection (microscopically negative margin resection) for 62% and R1 resection (removal of all macroscopic disease, but microscopic margins are positive for tumor) for 38% and with negative lymph nodes in 46% of the patients. The primary disease sites were extrahepatic cholangiocarcinoma (35%), hilar (28%), intrahepatic (19%), and muscle-invasive gallbladder cancers (18%). Patients were randomized in a 1:1 ratio to receive XELODA® 1250 mg/m2, D1-14 every 21 days, for 8 cycles or Observation. The median age was 63 years and the follow up was at least 36 months in more than 80% of the surviving patients. The primary end point was Overall Survival in the Intent to Treat population and the primary analysis was performed with at least 24 months of follow up.
The median Overall Survival with XELODA® was 51 months compared with 36 months for Observation, and this was not statistically significant (P=0.097). In the sensitivity analyses however, with adjustment for nodal status, gender and grade of the disease, there was a 29% reduction in the risk of death with adjuvant XELODA®, when compared with Observation (HR=0.71; P < 0.01). In the per-protocol analysis which included 430 patients, the median Overall Survival was 53 months with adjuvant XELODA® versus 36 months with Observation, resulting in a 25% reduction in the risk of death with XELODA®, and these results were statistically significant (HR=0.75; P=0.028). The most common adverse events related to XELODA® as anticipated were, palmar plantar erythema, fatigue and diarrhea.
The authors concluded that single agent XELODA® improves Overall Survival in Biliary Tract Cancer, when used as adjuvant therapy, without a negative impact on Quality of Life. They added that this is the first phase III study to show a survival benefit in the adjuvant setting, and should become standard of care. Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study. Primrose JN, Fox R, Palmer DH, et al. J Clin Oncol 35, 2017 (suppl; abstr 4006)