ORLANDO, FL—The combination of gemcitabine and cisplatin should be the standard of care for patients with advanced or metastatic biliary tract cancer, researchers said at the ASCO Annual Meeting here. In the Phase III UK ABC-02 trial, the doublet significantly reduced the risk of death by 30% compared with gemcitabine alone, said Juan W. Valle, MD, Senior Lecturer at the University of Manchester and a medical oncologist at Christie Hospital in Manchester, England.
“This is the first demonstration of survival benefit in biliary tract cancer. Cisplatin-gemcitabine is now the worldwide standard of care and the backbone for further studies.”
Moreover, he emphasized, the survival benefit in the study, the largest ever in advanced biliary tract cancer, was gained with no additional clinically significant toxicity.
Speaking at a teleconference in advance of the meeting, Dr. Valle said that currently there is no standard anti-tumor therapy for advanced biliary tract cancer: “Surgery is the only chance of a long-term cure, but the five-year survival rate is only five to 10 percent.”
Previous studies testing various therapies were limited by small series of older persons, often with serious comorbidities and sometimes complicated by infection or obstruction, and the lack of multicenter collaborations, he said.
Data on chemotherapy were derived from studies of heterogeneous populations treated primarily with fluorouracil and gemcitabine-based regimens. Additionally, randomized studies were underpowered, he said.
At the 2006 Gastrointestinal Cancers Symposium, Dr. Valle and colleagues reported results of a randomized Phase II trial of 86 patients showing that gemcitabine plus cisplatin may be associated with improved response rates, tumor control rates, time-to-progression, and progression-free survival rates, compared with gemcitabine alone (Abstract 98).
“However, limited patient numbers precluded statistical comparison, and it was unclear whether these improvements would translate into a survival benefit,” he and his coresearchers concluded at that time.
The trial was therefore expanded to include 410 patients at 34 centers, randomized in a one-to-one fashion to either 1,000 mg/m2 of gemcitabine on Days 1, 8, and 15, every 28 days, or 25 mg/m2 of cisplatin followed by 1,000 mg/m2 of gemcitabine on Days 1 and 8, every 21 days, for 24 weeks.
Patients were stratified by center, primary site, performance status, prior therapy, and extent of disease (locally advanced versus metastatic).
At a median follow-up period of 6.3 months, the median overall survival time was 11.7 months for patients treated with the doublet vs 8.3 months for patients who received gemcitabine monotherapy.
The difference in survival rates was significant, with a p value of 0.002, Dr. Valle said.
Additionally, the median progression-free survival time was 8.5 months in the combination arm vs 6.5 months in the gemcitabine-alone arm. This translated to a significant 30% reduction in risk of recurrence in the combination arm.
‘Definitive Trial in Difficult- to-Treat Disease’
ASCO 2008-2009 President Richard L. Schilsky, MD, Professor of Medicine and Associate Dean for Clinical Research at the University of Chicago, congratulated the researchers on a “definitive trial in a difficult-to-treat disease.
“As a physician who treats such patients, [I find it] very comforting to have a clear standard of care to offer them,” he said.
Dr. Valle said the next step will be to determine whether adding targeted drug therapy can further improve survival rates in these patients.