Patients who have undergone complete resection of biliary tract cancers live longer if they receive the oral chemotherapy agent capecitabine instead of simple observation, according to findings of the phase III randomized controlled BILCAP trial.

“The only curative treatment [for these cancers] is surgical resection, but even in that circumstance, most patients will ultimately succumb to the disease,” lead study author John N. Primrose, MD , professor of surgery at the University of Southampton (England), said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.

Results of the trial showed that compared with observation, capecitabine prolonged survival by a nonsignificant 15 months in the intention-to-treat population but by a significant 17 months in the per-protocol population. The drug had modest toxicity consistent with past experience and little impact on quality of life.

“On this basis, we believe that capecitabine should now become the standard of care for patients following curative resection of biliary tract cancer,” Dr. Primrose maintained.

The trial took place in a U.K. population, noted ASCO President Daniel F. Hayes, MD , clinical director of the breast oncology program and Stuart B. Padnos Professor in Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.

“This is a cancer that is much more common in Asia than it is in the western world, and I think that will be one of the questions that will be raised, as to whether these [results] apply to patients from Asia with the same cancer,” he said. “Otherwise, this is an impressive study, an enormous amount of work, and a very important finding.”

Study coauthor John A. Bridgewater, PhD , a professor at University College Hospital in London, said that he was not concerned that the trial missed its primary endpoint.

“It would of course have been much nicer if it had been significant, but I don’t think there is any doubt that there is a genuine effect here,” he maintained, agreeing that capecitabine should be standard of care going forward.

Other chemotherapies have made their way into similar adjuvant trials since BILCAP began, including the combination of cisplatin and gemcitabine being tested in the randomized ACTICCA-1 trial, Dr. Bridgewater acknowledged. “We’ve been discussing the possible permutations if BILCAP turned out to be positive with [those investigators], and that study, cisplatin-gemcitabine compared to surveillance, will now be modified to cisplatin-gemcitabine versus capecitabine. We came to that agreement some time ago.”

The BILCAP investigators are undertaking biomarker analyses of patients’ tumors. “The genotype of a bile duct cancer that will do well with fluoropyrimidine [such as capecitabine] is unknown, and that is exactly what we’ll be looking at when we look at the material. That surely will be one of the most important questions,” he said.

At present, there is no evidence to suggest that biliary tract cancers arising in Asian populations, which are mainly due to chronic infection with liver flukes, will differ in their response to capecitabine, according to Dr. Bridgewater.

“Certainly, you’ll be able to see in the clinical subgroup analyses, the long and the short of it is that it’s actually very difficult to distinguish, certainly on clinical grounds, any group that benefits more than other groups,” he said. “So the short answer is, there shouldn’t be any difference. But do we really know? Not yet.”

Study details

Patients enrolled in BILCAP had macroscopically completely resected cholangiocarcinoma or gallbladder cancer (including liver and pancreatic resection, as appropriate). They were randomized evenly to eight cycles of capecitabine (Xeloda) at a conventional dose or observation (Capecitabine is approved by the Food and Drug Administration for treatment of breast and colorectal cancers).

With more than 80% of patients having at least 3 years of follow-up, median overall survival in the intention-to-treat population – the trial’s primary endpoint – was 51 months with capecitabine and 36 months with observation (hazard ratio [HR], 0.81; P = .097), Dr. Primrose reported. The benefit became significant in a sensitivity analysis that adjusted for prognostic factors (HR, 0.70; P = .007).

In addition, median overall survival in the per-protocol population was significantly longer with capecitabine, at 53 months, than with observation, at 36 months (HR, 0.75; P = .028).

Median recurrence-free survival in the intention-to-treat population was 25 months for the capecitabine group and 18 months for the observation group.

“The toxicity associated with chemotherapy was relatively modest and in fact very similar to what has been observed in other studies,” Dr. Primrose said. The predominant grade 3 or 4 toxicity seen with capecitabine was plantar-palmar erythema, which occurred in 20.7% of patients who received the drug. There were no capecitabine-related deaths.

“Our quality of life analysis showed that there was very little difference in quality of life related to chemotherapy over those who did not have chemotherapy,” he added.

Dr. Primrose reported that he had no disclosures. Dr. Bridgewater disclosed ties with Merck Serono, Servier, Roche, Celgene, and MSD Oncology.