A phase III randomised clinical trial of 447 patients with biliary tract cancers (BTCs, cancers of the bile duct and gallbladder) showed that giving capecitabine after surgery extends survival by a median of 15 months compared to surgery alone.

The finding could provide the basis for a new standard of care in the disease.

This trial, called BILCAP, is one of the first randomised studies of adequate size to look at the use of adjuvant therapy in this rare and hard-to-treat cancer.

The study will be presented at the upcoming 2017 ASCO Annual Meeting in Chicago.

“Biliary tract cancer is a disease of decidedly unmet need as until recently there has been little research on treating the disease,” said lead study author John N. Primrose, MD, Professor of Surgery at the University of Southampton, United Kingdom. “Our trial is the first to enroll a sufficient number of patients to show that chemotherapy after surgery can have a significant improvement in survival, with modest side effects.”

Bile ducts inside and outside of the liver and gallbladder comprise the biliary tract.

The tract conducts and stores bile, a product of the liver that helps digest fat.

Patients with biliary tract cancers face considerable odds in that only about 20% of such cancers can be surgically removed, and for those that have a successful surgery, fewer than 10% survive five years.

At the time the trial was designed in the U.K. there was no standard of care for adjuvant therapy in BTC.

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, two chemotherapy agents in combination, gemcitabine and cisplatin, have evolved to be the current standards of care in the setting of advanced BTC on the basis of results from other studies done in the U.K.

In the trial, 447 patients were randomly assigned to either treatment with capecitabine for 6 months or observation for recurrence of cancer.

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 tumours.

While patients in the observation group lived a median of 36 months after surgery, those who received capecitabine lived a median of 51 months.

Capecitabine was associated with a 20% lower chance of death than observation, but the difference was not statistically significant for the overall population of 447 patients in this study, which includes patients that stopped capecitabine early.

However, in the subgroup of 430 patients that received treatment per study protocol, capecitabine was associated with a 25% lower chance of death than observation, and this difference was statistically significant.

The median time to cancer recurrence was 25 months for patients who received capecitabine and 18 months for patients in the control group.

The most notable side effect related to treatment was a rash on the hands and feet, which is common with capecitabine.

There were no deaths due to the use of capecitabine.

“One of the major benefits of our trial is the fact that we now have a tumour tissue collection associated with very robust clinical data which will be used for genomic exploration,” said Dr. Primrose. “Since we started planning this trial at the start of this century, a number of new agents have become available, including several that treat cancer based on its genetic profile. This is where our tumour tissue repository will play an important role.”

Dr. Primrose emphasised, however, that new approaches are urgently needed to develop and recruit patients for clinical trials in biliary cancer, as this trial’s ten-year timeline is much too long to conduct a trial in a rapidly evolving era of treatments and approaches.

International cooperation is desperately needed, he noted.

The authors are currently working on a subgroup analysis as there are four distinct types of BTC – three of which involve the liver and its ducts and one of which involves the gallbladder.

This analysis may help define more precisely which patients could benefit the most from adjuvant chemotherapy.

Source: ASCO 2017