Adjuvant chemotherapy with gemcitabine and cisplatin compared to standard of care after curative intent resection of cholangiocarcinoma and gallbladder carcinoma (ACTICCA-1 trial)

doi:10.1016/j.annonc.2026.10.1278

ACTICCA-1

Patient / Population Intervention / Exposure Comparison Outcome

In patients with resected biliary tract cancer, adjuvant gemcitabine and cisplatin did not significantly improve disease-free survival by log rank test compared with capecitabine, although restricted mean survival time favoured the combination.

N

591patients

Design

Randomised, phase III, investigator-initiated trial at 60 sites in 7 countries comparing 24 weeks of adjuvant gemcitabine and cisplatin with 24 weeks of capecitabine after curative intent resection of cholangiocarcinoma or gallbladder carcinoma (NCT02104882).

Endpoint

Disease-free survival in the full analysis set.

ResultMedian disease-free survival 2.14 vs 1.49 years with capecitabine (log rank p=0.097). The proportional hazard assumption was violated, so as pre-defined the Cox model (HR 0.82, 95% CI 0.67-1.01) was not feasible and restricted mean survival time was analysed: patients on gemcitabine and cisplatin had on average 2.6 additional DFS months (RMST in the first 3 years p=0.01). Overall survival showed a strong trend (p=0.076). Severe adverse events 130 vs 113, of which 51 vs 47 were treatment related. Adverse events occurred in 74.4% vs 69.5% of patients. Median follow-up was 4.8 years.

Stein A, Bridgewater J, Klümpen H, et al. Annals of Oncology. 2026. 10.1016/j.annonc.2026.10.1278

Discussion & critique

The primary log rank comparison of disease-free survival did not reach conventional significance (p=0.097) and the hazard ratio CI crosses 1, so the positive signal rests on the pre-specified restricted mean survival time analysis, which shows a modest average gain of 2.6 months over 3 years. Follow-up is mature at a median of 4.8 years, but overall survival is reported only as a trend with a P value and no arm figures. Toxicity was slightly higher with gemcitabine and cisplatin, and quality of life and recurrence patterns are left for the meeting. The abstract does not state whether the trial was blinded, and its conclusion that the regimen is a treatment option, not a new standard, matches the borderline data.