Oral fluoropyrimidine prolongs survival as adjuvant therapy for bile duct cancer

In a phase 3 study, patients with bile duct cancer who received an adjuvant oral fluoropyrimidine derivative S-1 lived longer than patients who underwent surgery.

Adjuvant oral fluoropyrimidine derivative S-1 is now a recommended standard of care for patients with biliary tract cancer after the agent prolonged overall survival compared to surgery in a phase 3 study (UMIN000011688 ).

Results presented at the 2022 Gastrointestinal Cancer Symposium showed that the 3-year overall survival (OS) rate was 77.1% (95% CI, 70.9%-82.1%) with S -1 and 67.6% (95% CI, 61.0%-73.3%) with surgery alone (RR, 0.694; 95% CI, 0.514-0.935; unilateral P = 0.008). Patients also had better 3-year relapse-free survival with S1 at 62.4% (95% CI, 55.6%-68.4%) and 50.9% (95% CI, 44.1 %-57.2%), respectively (HR, 0.797; 95% CI, 0.613-1.035).

“S-1 adjuvant therapy resulted in significantly longer survival than surgery alone in patients with resected BTC,” said Masafumi Ikeda, MD, PhD, of the National Cancer Center Hospital East, during the presentation.

A total of 440 patients were recruited into the study, including 222 in the surgery-only arm and 218 in the S-1 arm. Those receiving S-1 received 40 mg/m2 twice daily for 4 weeks on 2 weeks off for a total of 4 cycles. Patients were eligible for this study if they had curatively resected bile duct cancer, were between the ages of 20 and 80, and had a performance score of 0 or 1.

Patients receiving S-1 had a median age of 68 versus 70 for surgery alone, and most patients in both groups were male (74% versus 68%) and had an ECOG performance score of 0 ( 88% versus 87%) . Primary tumor site was most likely extrahepatic (57% versus 55%), followed by ampulla of vater (17% versus 16%), gallbladder (14% versus 15%) and intrahepatic (12% versus 14% ) in the S-1 and surgery-only arms, respectively.

Most patients in the S-1 and surgery groups had R0 resection status (86% versus 85%, respectively) and stage II disease (58% versus 59%), followed by stage III (17% versus 17%), stage I (16% versus 16%) and stage IV (9% versus 8%). Most patients had no lymph node involvement (N0; 61% versus 59%).

Analysis of OS by subgroup predominantly favored S-1 over surgery alone, including those with ECOG performance scores of 0 (0.70; 95% CI, 0.51-0, 97; P = 0.0632) and 1 (0.85; 95% CI, 0.39-1.85) as well as those with extrahepatic (0.80; 95% CI, 0.54-1.17; P = 0.5344), ampulla of vater (0.49; 95% CI, 0.22-1.12; P = 0.3041), gallbladder (0.64; 95% CI, 0.30-1.35) and intrahepatic (0.75; 95% CI, 0.30-1.89; P = .5939) primary tumor sites.

The most common Grade 3 adverse reaction (AE) in the S-1 arm was neutrophil count decrease (14%) which occurred in only 1% of the surgery alone arm. Other common grade 3 AEs were anemia (4% vs 1%), white blood cell count decreased (3% vs less than 1%), aspartate aminotransferase increased (3% vs

Reference

Ikeda M, Nakachi K, Konishi M, et al. Adjuvant S-1 versus observation in curatively resected bile duct cancer: a phase III trial (JCOG1202: ASCOT). J Clin Oncol. 2022;40(supplement 4):382. doi:10.1200/JCO.2022.40.4_suppl.382

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