John N. Primrose, FMedSci
In the phase III BILCAP trial reported in The Lancet Oncology, John N. Primrose, FMedSci, and colleagues found evidence that adjuvant capecitabine may improve overall survival vs observation following surgery for patients with resected biliary tract cancer.
The open-label study included 447 patients from 44 UK sites with cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone macroscopically complete resection with curative intent. Patients were randomly assigned between March 2006 and December 2014 to receive capecitabine 1,250 mg/m2 twice daily on days 1 to 14 of 21-day cycles for eight cycles (n = 223) or observation (n = 224) within 16 weeks of surgery. Randomization was stratified for surgical center, site of disease, resection status, and performance status.
The primary outcome was overall survival in the intent-to-treat population; secondary outcomes included overall survival in the per-protocol population, which excluded ineligible patients and patients failing to complete at least one cycle of capecitabine. The per-protocol population included 210 patients in the capecitabine group and 220 in the observation group.
Median follow-up was 60 months. In the intent-to-treat analysis, median overall survival was 51.1 months in the capecitabine group vs 36.4 months in the observation group (adjusted hazard ratio [HR] = 0.81, P = .097). In a protocol-specified sensitivity analysis adjusting for stratification factors, nodal status, grade, and gender, the overall survival hazard ratio was 0.71 (P = .010) in favor of capecitabine. In the per-protocol analysis, median overall survival was 53 months vs 36 months (adjusted HR = 0.75, P = .028). In intent-to-treat analysis, median recurrence-free survival was 24.4 months vs 17.5 months. In per-protocol analysis, median recurrence-free survival was 25.9 months vs 17.4 months.
Adverse events were graded only in the capecitabine group. Grade 3 adverse events occurred in 44% of patients, with the most common being hand-foot syndrome (20%), diarrhea (8%), and fatigue (8%). Serious adverse events were observed in 21% of patients. No treatment-related deaths were reported.
The investigators concluded, “Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting.” ■