Adjuvant cisplatin-gemcitabine fails to significantly improve disease-free survival in biliary tract cancer
- **In a phase III trial of 591 patients with resected biliary tract cancer, the combination of cisplatin and gemcitabine did not statistically improve disease-free survival compared to capecitabine alone.
- CisGem showed a median DFS of 25.7 months compared to 17.9 months for capecitabine (log rank p=0.097).
- As pre-defined in the statistical analysis plan (SAP), due to violation of proportional hazard assumption a Cox model was not feasible and restricted mean survival time (RMST) was analysed.
The publication
**In a phase III trial of 591 patients with resected biliary tract cancer, the combination of cisplatin and gemcitabine did not statistically improve disease-free survival compared to capecitabine alone. The regimen showed a numerical gain in restricted mean survival time but increased severe adverse events, leading authors to advise against its use as standard adjuvant care.**
Who the findings apply to
Patients were enrolled at 67 sites across 8 countries between September 2017 and January 2023 and randomized to CisGem or capecitabine as adjuvant treatment regimen, each for a planned duration of 24 weeks.
Median age was 63, 46.9% were female, and median interval between surgery and enrolment was 67 days.
Primary tumour location was intrahepatic in 28.3%, perihilar in 19%, distal in 36.5%, and gallbladder in 16.2%, 47.9% of patients had lymph node positive disease (N+).
Why this matters
The study addresses the high recurrence rate of biliary tract cancer after curative surgery and adjuvant capecitabine. By testing whether the established palliative regimen of cisplatin plus gemcitabine (CisGem) offers superior disease-free survival, the trial aimed to identify a more effective adjuvant strategy. The authors conclude that because CisGem did not statistically improve disease-free survival compared to capecitabine, it should not be applied as standard of care in this setting.
What the study found
591 patients have been randomized. Median follow-up was 4.8 years.
CisGem showed a median DFS of 25.7 months compared to 17.9 months for capecitabine (log rank p=0.097).
As pre-defined in the statistical analysis plan (SAP), due to violation of proportional hazard assumption a Cox model was not feasible and restricted mean survival time (RMST) was analysed.
Patients receiving CisGem experienced on average 2.6 additional DFS months (95% CI 0.6-4.68) compared to capecitabine (RMST in the first 3 years, p=0.011), but no significant improvement in overall survival (RMST p=0.076; median 58.1 vs. 48.2 months).
What the result does not establish
Toxicity showed a higher number of Severe Adverse Events (SAE) (130 vs. 113 with 51 vs. 47 assessed as treatment related) and a higher AE rate of 74.7% vs. 69.5% with CisGem compared to capecitabine.
CisGem did not statistically improve DFS compared to capecitabine and should thus not be applied as standard of care in the adjuvant setting.
Authors’ conclusion
“CisGem did not statistically improve DFS compared to capecitabine and should thus not be applied as standard of care in the adjuvant setting.”
Trial registration
Registered with the trial registry as 2024-517340-61-00. ENCLAI does not hold this registry record, so its details are not shown; follow the link to read it.
| Registered title | INTRAGO-Intraoperative Radiotherapy for Glioblastoma - a Phase I/II Study |
|---|---|
| Registry status | Phase 1 / Phase 2, interventional, completed |
| Lead sponsor | Universitätsmedizin Mannheim |
| Registered size | 12 participants — actual enrolment |
| Where | 1 site in 1 country (Germany) |
| Registered primary outcome |
Primary endpoint named in the abstract: disease-free survival (DFS). Compare the two: a change of primary endpoint after registration matters. |
- Start: Mar 2014
- Completion: Sep 2016
- Primary completion: Sep 2016
- Paper published: Oct 2026
ClinicalTrials.gov record as held by ENCLAI, last updated Oct 2016. The registry status may have changed since; the link shows the current record.
Study and sources
Adjuvant chemotherapy with cisplatin and gemcitabine compared to standard of care after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1/AIO-HEP-0112 trial)
Randomised trial · Phase 3 · Annals of oncology · 2026-10-24
Sources and limitations
- PubMed record PMID 42926109 (PubMed / NLM · 2026-11-08)
- Trial registry NCT02104882 (ClinicalTrials.gov · 2026-11-08)
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