Durvalumab plus gemcitabine and cisplatin has become a standard first-line treatment for advanced biliary tract cancer based on the primary and longer-term follow-up analyses of the phase 3 TOPAZ-1 trial. A final post hoc analysis now reports long-term survival, subsequent anticancer therapy use, and safety outcomes at a data cutoff approximately four years after the last participant was randomized.
The analysis showed that the survival benefit associated with adding durvalumab to chemotherapy was maintained with extended follow-up. At 48 months, the estimated overall survival rate was 11.8% with durvalumab plus gemcitabine and cisplatin, compared with 4.3% with placebo plus gemcitabine and cisplatin.
The article, titled “Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial,” was published online in JAMA Oncology on July 9, 2026.
Authors: Do-Youn Oh, Aiwu Ruth He, Shukui Qin, Li-Tzong Chen, Takuji Okusaka, Rebecca Griffin, Julie Wang, Ioannis Xynos, Arndt Vogel, and Juan W. Valle.
TOPAZ-1 Study Design
TOPAZ-1 was a global, double-blind, placebo-controlled, phase 3 randomized trial that enrolled adults with histologically confirmed unresectable, locally advanced, or metastatic biliary tract adenocarcinoma. Between April 2019 and December 2020, 685 participants were randomized across 105 sites in 17 countries. Participants were randomly assigned in a 1:1 ratio to receive:
- Durvalumab plus gemcitabine and cisplatin: 341 patients
- Placebo plus gemcitabine and cisplatin: 344 patients
Durvalumab was administered intravenously at a dose of 1500 mg. Gemcitabine was given at 1000 mg/m² and cisplatin at 25 mg/m² on days 1 and 8 of each 21-day cycle for up to eight cycles. This was followed by durvalumab or placebo monotherapy every four weeks until a treatment-discontinuation criterion was met.
Randomization was stratified according to disease status and primary tumour location, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
The final data cutoff was February 28, 2025, approximately 48 months after the last participant was randomized.
Read more about Durvalumab (Imfinzi) on OncoDaily.
Survival Benefit Maintained With Four-Year Follow-Up
Among censored participants, the median duration of follow-up was 56.9 months in the durvalumab group and 50.7 months in the placebo group.
Median overall survival was:
- 13.0 months with durvalumab plus gemcitabine and cisplatin
- 11.4 months with placebo plus gemcitabine and cisplatin
The hazard ratio for death was 0.75, corresponding to a 25% lower risk of death with the durvalumab-containing regimen.
The survival benefit with durvalumab plus GemCis was maintained during long-term follow-up. Overall survival rates with durvalumab plus GemCis versus placebo plus GemCis were:
- At 24 months: 23.2% versus 13.7%
- At 36 months: 15.0% versus 7.6%
- At 48 months: 11.8% versus 4.3%
The 48-month overall survival rate ratio was 2.74 in favour of durvalumab plus GemCis. The observed overall survival benefit across clinically relevant subgroups was generally consistent with that reported in earlier TOPAZ-1 analyses. At the final data cutoff, seven patients in the durvalumab group remained on any study treatment, compared with none in the placebo group.
Subsequent Treatment Use
The overall use of subsequent anticancer therapy was similar between the two treatment groups, with cytotoxic chemotherapy representing the most frequently administered subsequent treatment.
Subsequent immunotherapy was received by 3.8% of patients initially treated with durvalumab plus chemotherapy and 8.1% of those initially assigned to placebo plus chemotherapy.
Rechallenge with durvalumab plus gemcitabine and cisplatin was uncommon, occurring in four patients in the durvalumab group and one patient in the placebo group.
Long-term Safety Remained Consistent
The safety analysis included 338 patients who received durvalumab plus chemotherapy and 342 who received placebo plus chemotherapy.
The median duration of durvalumab or placebo exposure was 7.3 months and 5.8 months, respectively. Rates of serious adverse events considered possibly related to treatment were comparable between the groups:
- 15.4% with durvalumab plus chemotherapy
- 17.3% with placebo plus chemotherapy
Adverse events leading to discontinuation of durvalumab or placebo occurred in 6.2% and 5.3% of patients, respectively.
The most common serious adverse events in the durvalumab group included cholangitis, pyrexia, anaemia, and sepsis. Immune-mediated adverse events occurred more frequently with durvalumab than with placebo, at 30.2% and 20.8%, respectively.
No new safety signals were identified with prolonged follow-up. Since the previous three-year analysis, there were no additional adverse events leading to treatment discontinuation and no newly reported serious adverse events considered possibly related to study treatment.
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Limitations of the Final Analysis
The authors noted that the four-year evaluation was a post hoc analysis and that all assessments were exploratory, with no formal statistical calculations. No progression-free survival data were included because progression-free survival was already mature at the primary data cutoff. Tumour-response data were therefore no longer collected.
In addition, after the trial’s 90-day safety follow-up period, only serious adverse events and adverse events resulting in treatment discontinuation were reported.
Conclusion
The final post hoc analysis of TOPAZ-1 showed that the overall survival benefit associated with adding durvalumab to gemcitabine and cisplatin was maintained during long-term follow-up in patients with advanced biliary tract cancer.
Median overall survival was 13.0 months with durvalumab plus GemCis and 11.4 months with placebo plus GemCis. At 48 months, the estimated overall survival rates were 11.8% and 4.3%, respectively.
Together with the absence of new long-term safety signals, these findings continue to support durvalumab plus gemcitabine and cisplatin as a first-line standard-of-care treatment for advanced biliary tract cancer.
The full article is available in JAMA Oncology.
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