New results from a phase 3 trial in patients with biliary tract cancer "will change practice overnight," says an expert not involved in the trial.
The new data will be presented at the forthcoming American Society of Clinical Oncology (ASCO) 2017 Annual Meeting in Chicago, but were highlighted today in a premeeting presscast.
The results come from the British BILCAP study and show that adjuvant capecitabine (Xeloda, Hoffman-LaRoche), used for 6 months after surgery for biliary tract cancer, improved median overall survival by 15 months when compared to observation after surgery (51 months vs 36 months).
"Capecitabine is already available and is widely used, and clinicians are comfortable using this drug, and so I expect that these new results will lead to an overnight change in practice," Richard Schilsky, MD, chief medical officer at ASCO and former chief of the Section of Hematology-Oncology at the University of Chicago, told Medscape Medical News.
Another expert not involved in the study was equally enthusiastic. "I agree that these are very impressive results," commented Boris Blechacz, MD, PhD, from the Department of Gastroenterology, Hepatology and Nutrition at the University of Texas MD Anderson Cancer Center in Houston.
"BILCAP is one of the very few randomized controlled phase 3 trials evaluating adjuvant chemotherapy in the setting of biliary tract cancers. It is one of the largest trials with a high number of patients. The results and their statistical significance are persuasive. These results, as presented in the abstract, are very impressive and could change the management of biliary tract cancers," Dr Blechacz told Medscape Medical News.
The standard approach, and the only curative approach, to biliary tract cancer is surgery, but on presentation, only about 20% of patients are suitable for surgical resection.
When the BILCAP study began 10 years ago, the standard of care after biliary tract surgery was observation. The investigators, led by John Primrose, MD, professor of surgery at the University of Southampton, United Kingdom, designed the trial to test whether adding adjuvant chemotherapy would improve the outcome. They chose to use capecitabine because it could be given as a tablet and also because it had shown efficacy in the treatment of pancreatic cancer, a disease with similarly poor outcomes.
The trial enrolled 447 patients at various sites across the United Kingdom. More than 80% of the patients were followed for at least 3 years with regular clinical examinations, CT imaging, and a variety of blood tests.
Patients were randomly assigned in a 1:1 ratio to adjuvant therapy or observation. Capecitabine was taken orally at a dose of 1250 mg/m2 twice daily on days 1 to 14 every 21 days for 8 cycles.
In the overall population of 447 patients, the difference in median overall survival (51 months on capecitabine vs 36 months on observation) did not reach statistical significance (hazard ratio [HR], 0.80; P = .097).
However, some of the patients in the capecitabine group stopped taking the drug early.
In the large subgroup of 430 patients who took capecitabine for 6 months as per the study protocol, the difference was statistically significant: the median overall survival was 53 months with capecitabine and 36 months with observation (HR, 0.75; P = .028).
When asked about the lack of statistical significance in the intent-to-treat population, senior author John Bridgewater, MD, from the University College London Cancer Institute, commented that this was not a concern. "The effect size is dramatic, and there is no doubt that this is a genuine effect," he said.
Dr Bridgewater, who spoke at the presscast, also said that the toxicity seen was "relatively modest" and that 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 caused by the drug.
He also noted that because biliary tract cancer is uncommon, the accrual period for the BILCAP study was long ― from 2006 to 2014. While the trial was in progress, results from another trial conducted in the United Kingdom showed that the combination of gemcitabine and cisplatin was beneficial for patients with advanced biliary tract cancer. A trial currently in progress is investigating this combination in the adjuvant setting, Dr Bridgewater noted. In that trial, the chemotherapy combination was being tested against observation, but the trial was recently amended to include a new arm with adjuvant capecitabine. Results from that trial are some years away.
For now, adjuvant capecitabine should be considered the standard of care for patients who undergo resection for biliary tract cancer, Dr Bridgewater said.
The 447 patients enrolled in the BILCAP study had undergone complete resection of CCA or gallbladder cancer (including liver and pancreatic resection, as appropriate). Of the 447 patients, the primary site was intrahepatic in 84 patients (19%) and hilar in 128 (28%) patients; 156 (35%) patients had extrahepatic CCA; and 79 (18%) had muscle-invasive gallbladder cancers.
The UK researchers noted that they are currently working on a subgroup analysis of the different types of bile ducts that were involved to see whether patients with a particular type of biliary tract cancer benefitted more than others. In addition, the team has collected tumor tissue, and there are "very robust clinical data which will be used for genomic exploration," Dr Primrose added.
Commenting on the study, Dr Blechacz told Medscape Medical News: "While care was taken to have a fairly even distribution of the different types of biliary tract cancers, it will be important to see the subgroup analyses."
He noted that previous studies have shown that the location may affect the outcome. "For example, the ESPAC-3 trial has shown that adjuvant chemotherapy had a statistically significant survival benefit in patients with periampullary carcinoma only after adjusting for independent prognostic factors. The current study also includes periampullary carcinomas, and it would be interesting to see the effect in this current study. An older Japanese study (506 patients, randomized controlled trial) did not find a benefit of adjuvant chemotherapy in periampullary and cholangiocarcinoma but [did find benefit] in gallbladder carcinoma."
"Biliary tract cancer is a disease of decidedly unmet need, as until recently, there has been little research on treating the disease," Dr Primrose commented in a statement. "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."