Curative resection remains the only potential route to long-term survival in extrahepatic cholangiocarcinoma (eCCA), yet postoperative recurrence is frequent. Adjuvant capecitabine is widely used following resection, based on evidence from the BILCAP trial. Nonetheless, recurrence rates remain high, underscoring the limitations of chemotherapy alone in the adjuvant setting. Immune checkpoint inhibitors have improved outcomes in advanced biliary tract cancer, as shown in the TOPAZ-1 and KEYNOTE-966 trials, prompting interest in evaluating immunotherapy earlier in the disease course. This phase 2 study (NCT05207735) was designed to evaluate the efficacy and safety of adjuvant sintilimab, an anti–programmed cell death protein 1 antibody, in combination with capecitabine in patients who underwent resection for eCCA.
Eligible participants were aged 18 to 75 years with histologically confirmed primary eCCA and had undergone either R0 (complete resection) or R1 (microscopic residual disease) surgery. All patients had an ECOG Performance Status of 0 or 1. The adjuvant regimen consisted of sintilimab 200 mg administered intravenously every 3 weeks for 6 cycles, along with capecitabine 1250 mg/m2 orally twice daily for 14 days every 3 weeks over 8 cycles. The primary endpoint was 2-year recurrence-free survival (RFS); secondary endpoints included 1-year RFS, 2- and 3-year overall survival (OS), and safety.
Interim results from 31 patients with a median follow-up of 20.0 months (range, 5.8-51.8) showed a 2-year RFS rate of 72.8%, with OS being 75.5% at 2 years and 68% at 3 years. Most patients (83.9%) had a R0 resection. Treatment-related adverse events (TRAEs) occurred in 74.2% of patients; the most frequently reported TRAEs were anorexia (41.9%), fatigue (25.8%), nausea/vomiting (22.6%), hand-foot syndrome (22.6%), and skin rash (19.4%). Grade ≥3 TRAEs were observed in 16.1%, and no treatment-related deaths occurred.
These findings suggest that sintilimab combined with capecitabine as adjuvant therapy has the potential to improve RFS in patients with resected eCCA while maintaining a manageable safety profile. These results warrant further investigation in randomized trials to confirm the efficacy and expand clinical applications of this regimen in high-risk patients.
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