ASCO 2017: Adjuvant Capecitabine May Extend Survival in Biliary Tract Cancer

Key Points

  • Patients in the observation group lived a median of 36 months after surgery. Those who received capecitabine lived a median of 51 months.
  • The median time to cancer recurrence was 25 months for patients who received capecitabine and 18 months for patients in the control group.
  • In the subgroup of 430 patients who received treatment per study protocol, capecitabine was associated with a 25% lower chance of death than observation, and this difference was statistically significant. 

A phase III randomized clinical trial in 447 patients with biliary tract cancers showed that treating the disease with 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 randomized 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 by Primrose et al at the upcoming 2017 ASCO Annual Meeting in Chicago (Abstract 4006).

Study Background

“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 produce a significant improvement in survival, with modest side effects.”

Only about 20% of biliary tract cancers can be surgically removed, and for those who have a successful surgery, fewer than 10% survive 5 years. Biliary tract cancers are becoming more and more common in Asian countries.

At the time the trial was designed, there was no UK standard of care for adjuvant therapy in biliary tract cancer. Capecitabine was chosen out of several commonly used systemic therapies because it could be given orally and had shown efficacy in pancreatic cancer, a disease with similarly poor outcomes. Subsequent to the start of the trial, a combination of two chemotherapy agents—gemcitabine and cisplatin—has become the standard of care in advanced biliary tract cancer on the basis of results from other studies done in the UK.

Key Findings

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 3 years with regular clinical exams, computed tomography imaging, and a variety of blood tests that could be useful later in determining biomarkers for tumors.

Patients in the observation group lived a median of 36 months after surgery, whereas 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 the study, which includes patients who stopped capecitabine early. However, in the subgroup of 430 patients who 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.

Next Steps

“One of the major benefits of our trial is the fact that we now have a tumor tissue collection associated with 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 tumor tissue repository will play an important role.”

Dr. Primrose emphasized, however, that new approaches are urgently needed to develop and recruit patients for clinical trials in biliary cancer, as this trial’s 10-year timeline is much too long to conduct a trial in an era of rapidly evolving 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 biliary tract cancers, three of which involve the liver and its ducts, and one that involves the gallbladder. This analysis may help define more precisely which patients could benefit the most from adjuvant chemotherapy.

Commentary

“This study helps resolve long-standing questions about adjuvant treatment for biliary tract cancer, for which there has been no standard of care,” said ASCO President Daniel F. Hayes, MD, FACP, FASCO. “This oral chemotherapy is widely available and can offer patients the chance to live more than a year longer.”

This study received funding from Cancer Research UK.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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