Capecitabine Remains SOC in Biliary Tract Cancer After Long-Term BILCAP Study Update

The 5-year survival data from the BILCAP study (NCT00363584) support the use of capecitabine (Xeloda) in patients with biliary tract cancer (BTC) when used as adjuvant chemotherapy after surgery as it has shown to improve overall survival (OS) in these patients. Investigators consider capecitabine as the standard of care for patients in this circumstance.¹

Between March 15, 2006, and December 4, 2014, 447 patients with BTC with curative intent were randomized 1:1 to receive capecitabine (n = 223) or to an observation group (n = 224). The median OS was 49.6 months (95% CI, 35.1-59.1) in the capecitabine group versus 36.1 months (95% CI, 29.7-44.2) in the observation group (adjusted hazard ratio [HR], 0.84; 95% CI, 0.67-1.06) in the intent-to-treat analysis (ITT). The data cutoff occurred on January 21, 2021, and the median follow-up for all patients was 106 months (95% CI, 98-108).

The BILCAP study is a randomized controlled, multicenter, phase 3 study. Investigators recruited patients 18 years or older with histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer after resection with curative intent who also had an ECOG performance status less than 2. Patients in the capecitabine group received 1,250 mg/m2 of oral capecitabine twice daily on days 1 to 14 of a 21-day cycle, for 8 cycles. The primary end point was OS. In a protocol-specified sensitivity analysis, adjusting for minimization factors, nodal status, grade, and sex, the OS hazard ratio was 0.74 (95% CI, 0.59-0.94).

In the ITT analysis, the median recurrence-free survival (RFS) was 24.3 months for the capecitabine group and 17.4 months for the observation group (HR, 0.81). The 5-year RFS proportion for the ITT population was 34% for patients receiving capecitabine and 31% for patients in the observation group.²

Poorer survival was seen in patients with R1 status compared with patients who had R0 status (HR, 1.60). Inferior survival results were also seen in patients with positive node status compared with negative (HR, 2.22), and poorly differentiated tumors compared with well-differentiated (HR = 1.90). Female patients saw better survival than in male patients (HR, 0.78). There was no evidence that either site of disease or ECOG performance status was associated with differential survival.

Investigators noted R1 resection in the observation arm are more likely to have a local recurrence alone (24 of 84, 29%) compared with R0 resections (27 of 140, 19%). Capecitabine did not appear to have any impact on the local recurrence rate for either R0 or R1 resections (26 of 139, 19% versus 25 of 84, 30%, respectively).

Advancements in the treatment of advanced BTC have been in the targeted therapy of alterations like FGFR, IDH1, BRAF, and others. The molecular description of the BILCAP study is currently underway and may provide further insights into the biology of individual subgroups and other prognostic variables. To emphasize the importance of cross-study collaboration, the analysis will be limited by the number of patients in each subgroup.²

The long-term analysis supports its previous analysis, suggesting that capecitabine can improve OS in patients with resected BTC when used as adjuvant chemotherapy after surgery. Capecitabine remains the adjuvant standard of care after curatively resected BTC.²

_References

_{1. Bridgewater J, Fletcher P, Palmer DH, et al. Long-term outcomes and exploratory analyses of the randomized phase III BILCAP study. Published online March 22, 2020. J Clin Oncol. 2022. doi:10.1200/JCO.21.02568}

_{2. Benefit of adjuvant capecitabine after curative resection of biliary tract cancer maintained with a long-term analysis. News release. ESMO Oncology News. April 6, 2022. Accessed April 7, 2022. https://bit.ly/3LLhfjU}