Based on results of the phase III BILCAP study, adjuvant capecitabine should become standard treatment for patients with biliary tract cancer. Among 430 patients who were treated according to the study protocol, capecitabine was associated with a 25% lower risk of death than observation.

The use of capecitabine following surgery in patients with biliary tract cancer should become standard treatment, according to researchers associated with the phase III BILCAP study. Researchers recently summarized their findings, which will be presented in full on June 4 at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.

According to the American Cancer Society, about 12,000 people are diagnosed with biliary tract cancer in the United States every year, and they have a poor prognosis with few treatment options. “The only curative treatment is surgical resection, but even in that circumstance, most patients will succumb to the disease,” said John Primrose, MD, professor of surgery at the University of Southampton in the UK and lead author of the study.

Primrose and his team wondered whether the adjuvant use of the oral chemotherapeutic capecitabine would improve survival and launched the BILCAP trial to answer the question. Over 8 years, they enrolled 447 patients in the trial, randomly assigning them to a treatment group in which they received capecitabine for 6 months, or to an observation group. More than 80% of the patients were followed for at least 3 years with clinical exams, CT imaging, and blood tests. Patients in the observation group lived a median of 36 months after surgery, whereas those who received capecitabine lived a median of 51 months. Treatment was associated with a 20% lower chance of death than observation, but that difference was not statistically significant.

“It would have been much nicer if it had been significant, but I don't think there's any doubt that there's a genuine effect here,” said John Bridgewater, MD, PhD, the study's senior author. However, he noted that several patients stopped taking capecitabine early; assessing the subset of 430 patients who were treated according to the study protocol, capecitabine was associated with a 25% lower risk of death than observation—a difference that was statistically significant. “On this basis, we believe capecitabine should become the standard of care for patients following curative resection of biliary tract cancer,” he added.

Primrose noted that the toxicity associated with capecitabine was relatively modest and similar to what has been observed in other studies. The most common grade 3/4 adverse event, which affected 20.7% of patients in the treatment group, was a rash on hands and feet. “There was very little difference in quality of life between those who had chemotherapy and those who didn't have chemotherapy,” he said.

When the BILCAP trial started in 2005, “there wasn't anything else on the map” to treat patients, said Bridgewater. Since then, a study published in 2010 in The New England Journal of Medicine concluded that the combination of cisplatin plus gemcitabine extended overall survival in patients with advanced biliary tract cancer by 3.6 months compared with gemcitabine alone. In an accompanying editorial, Brian Wolpin, MD, MPH, and Robert Mayer, MD, both from Dana-Farber Cancer Institute in Boston, called that finding “a definite step forward” and wrote that “the cisplatin–gemcitabine combination should be considered a standard treatment option.”

Whether that combination is more effective than capecitabine remains an open question. Currently, the European ACTICCA-1 trial is comparing the cisplatin–gemcitabine combination with observation following surgery, but given the positive results of BILCAP, researchers will likely modify the trial to test that combination against capecitabine instead, Primrose said.

Another question that remains unanswered, noted Daniel Hayes, MD, president of ASCO, is whether patients outside the UK—particularly in Asia, where biliary tract cancer is more common—would have similar responses to capecitabine.

Even so, Hayes concluded that “this is an impressive study, a tremendous amount of work, and an important finding.” –Suzanne Rose