Adjuvant capecitabine prolongs the survival of biliary tract cancer with more than 1 year

Results of the phase III, randomized BILCAP trial, including 447 patients with cancers of the bile duct, or gallbladder, showed that adjuvant capecitabine after surgery extends the median overall survival by a median of 15 months compared to surgery alone. Interestingly, adjuvant capecitabine was associated with modest side effects. As such, these findings provide the basis for a new standard of care for this disease.

Biliary tract cancer is a disease with a high unmet medical need. In fact, only about 20% of biliary tract cancers can be surgically removed, and for those that have a successful surgery, fewer than 10% survive five years. In the study at hand capecitabine was chosen out of several commonly used systemic therapies because it could be given as a tablet and had shown efficacy in pancreatic cancer, a disease with similarly poor outcomes. Subsequent to the start of the trial, the combination of gemcitabine and cisplatin evolved to be the current standard of care in the setting of advanced biliary tract cancer on the basis of other clinical studies.

In the trial, 447 patients were randomly assigned to adjuvant treatment with capecitabine for 6 months or observation. More than 80% of the patients were followed for at least three years with regular clinical exams, CT imaging, and a variety of blood tests that could be useful later in determining biomarkers for the tumors. While patients in the observation group lived a median of 36 months after surgery, those who received capecitabine lived a median of 51 months (HR[95%CI]: 0.80 [0.63, 1.04]; p= 0.097). As such, capecitabine was associated with a 20% lower chance of death than observation. However, this difference was not statistically significant for the overall study population. In the subgroup of 430 patients that received treatment per study protocol (i.e. excluding patients who stopped treatment prematurely), capecitabine was associated with a 25% lower chance of death compared to observation, and this difference was statistically significant (median overall survival: 53 versus 36 months; (HR{95%CI]: 0.75 [0.58, 0.97]; p= 0.02). The median time to cancer recurrence was 25 months for patients who received capecitabine and 18 months for patients in the control group (HR[95%CI]: 0.75 [0.58, 0.97]; p= 0.028). The median recurrence free survival was 25 months for capecitabine and 18 months for observation. The most notable side effect related to treatment was a rash on the hands and feet, which is common with capecitabine. However, the incidence of grade 3-4 toxicity was less than anticipated and there were no deaths due to the use of capecitabine.

The authors are currently working on a subgroup analysis looking at the four distinct types of biliary tract cancer. This analysis may help define more precisely which patients could benefit the most from adjuvant chemotherapy.

Reference

Primrose J, Fox R, Palmer DH, et al. Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study. Presented at ASCO 2017; Abstract 4006.