Capecitabine continued to improve overall survival (OS) in patients with resected biliary tract cancer (BTC) when used as adjuvant treatment after surgery, according to the long-term analysis of the BILCAP study published in the Journal of Clinical Oncology.
The phase 3 BILCAP trial was conducted at 44 centers in the United Kingdom and was designed to compare oral capecitabine with observation alone following curative resection of BTC.
Between March 15, 2006, and December 4, 2014, the study enrolled 447 patients with BTC resected with curative intent (intention-to-treat [ITT] population); 223 patients were randomly assigned 1:1 to receive oral capecitabine postoperatively (1250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for 8 cycles), and the remaining 224 patients were under observation, which commenced within 16 weeks of surgery.
For the long-term analysis (data cutoff, January 21, 2021), the median follow-up was 106 months (95% CI, 98-108). At that point, 65% of patients in the capecitabine arm and 71% in the observation arm had died.
In the ITT population, the median OS was 49.6 months in the capecitabine arm and 36.1 months in the observation arm (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.67-1.06). The median recurrence-free survival (RFS) was 24.3 months in the capecitabine arm and 17.4 months in the observation arm after adjusting for resection status, performance status, and site of disease (aHR, 0.77; 95% CI, 0.61-0.97).
In the per-protocol population (capecitabine, 210 patients; observation, 220 patients), the median OS was 52.3 months in the capecitabine arm and 36.1 months in the observation arm (aHR, 0.79; 95% CI, 0.63-1.0). The median RFS in the capecitabine and observation arms was 25.3 months and 16.8 months, respectively.
In a protocol-specified sensitivity analysis, the HR for OS was 0.74 (95% CI, 0.59-0.94) after adjusting for the effect of several prognostic factors, including nodal status, disease grade, sex, and minimization factors.
Researchers observed significantly worse survival in patients with R1 resection compared with R0 (HR, 1.60), positive node status compared with negative (HR, 2.22), and poorly differentiated tumors compared with well-differentiated (HR, 1.90). The data also showed better survival among women than among men (HR, 0.78).
In the observation arm, patients with R1 resections were more likely to have a local recurrence alone (29%), compared with those who had R0 resections (19%). However, in the capecitabine arm, R0 (19%) or R1 (30%) resections did not have an effect on the local recurrence rate.
According to the researchers, these data represent the single largest prospectively assembled data set of patients after curatively resected BTC, confirming the benefit of capecitabine as adjuvant therapy after surgical resection of BTC.
The main benefit from capecitabine appears to be in the timing of recurrence, the researchers noted. Recurrence tended to happen later among patients treated with capecitabine than among those under surveillance, providing an advantage in terms of both RFS and OS.
“Capecitabine remains effective and beneficial in this population regardless of subgroup classification,” the researchers concluded. “Capecitabine remains the adjuvant standard of care after curatively resected BTC and the control arm of future randomized studies.”
Disclosures: This research was partially supported by F. Hoffmann-La Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Bridgewater J, Fletcher P, Palmer DH, et al. Long-term outcomes and exploratory analyses of the randomized phase III BILCAP study. J Clin Oncol. Published online March 22, 2022. doi:10.1200/JCO.21.02568