TOPAZ-1
Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer
Phase 3N = 685NCT03875235
- Population
- Adults with previously untreated unresectable, locally advanced or metastatic biliary tract cancer, or recurrent disease
- Design
- Global, randomised (1:1), double-blind, placebo-controlled phase 3 trial at 105 sites in 17 countries. Durvalumab 1500 mg or placebo on day 1 of each 3-week cycle with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 for up to eight cycles, followed by durvalumab 1500 mg or placebo every 4 weeks until progression or other discontinuation criteria; stratified by disease status and primary tumour location. The primary objective was overall survival; secondary end points included progression-free survival, objective response rate and safety. 914 participants were enrolled and 685 randomly assigned.
- Primary endpoint
- OS
- Arms
- Durvalumab plus gemcitabine and cisplatin (experimental, n = 341): Durvalumab 1500 mg plus gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 every 3 weeks for up to eight cycles, then durvalumab 1500 mg every 4 weeks
- Placebo plus gemcitabine and cisplatin (control, n = 344): Placebo plus gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 every 3 weeks for up to eight cycles, then placebo every 4 weeks
- People
- Oh DY
OSHR 0.80 (95% CI 0.66–0.97)Δ 24-month OS+14.5 pointsOSHR 0.80 (95% CI 0.66–0.97)Δ median OS+1.3 monthsPFSHR 0.75 (95% CI 0.63–0.89)Δ ORR+8 points
Show the numbers
| Endpoint | Analysis | Durvalumab plus gemcitabine and cisplatin | Placebo plus gemcitabine and cisplatin | Effect |
|---|---|---|---|---|
| OSRandomly assigned patients (the abstract does not name the analysis set) | primaryOh 2022 | 24.9% at 2 y (17.9–32.5%) | 10.4% at 2 y (4.7–18.8%) | HR 0.80 (95% CI 0.66–0.97)P=0.021Deaths at data cut-off: 198 (58.1%) with durvalumab and 226 (65.7%) with placebo. The abstract gives no medians; the later TOPAZ-1 paper (Lancet Gastroenterol Hepatol 2024) describes the primary result as a preplanned interim analysis. Medians for this analysis are in the label-based result below. |
| OSRandomized patients, N=341 and N=344 (FDA prescribing information) | primarySource 2026 | median 12.8 months (11.1–14.0) | median 11.5 months (10.1–12.5) | HR 0.80 (95% CI 0.66–0.97)P=0.021Same analysis as the primary report (198 and 226 deaths), as tabulated in the FDA prescribing information (section 14.3, Table 33): Kaplan-Meier median with 95% CI by the Brookmeyer-Crowley method; two-sided stratified log-rank P value against an alpha boundary of 0.030. These medians are from the label text, not from the journal abstract. |
| PFSRandomly assigned patients (the abstract does not name the analysis set) | primaryOh 2022 | — | — | HR 0.75 (95% CI 0.63–0.89)P=0.001Secondary end point. The abstract gives no median progression-free survival. |
| ORRRandomly assigned patients (the abstract does not name the analysis set) | primaryOh 2022 | 26.7% | 18.7% | Secondary end point; the abstract gives no confidence intervals or P value for the objective response rates. |
| OSFull analysis set (all randomly assigned participants) | long term-updatemedian follow-up 23.4 monthsOh 2024 | median 12.9 months (11.6–14.1); 23.6% at 2 y (18.7–28.9%) | median 11.3 months (10.1–12.5); 11.5% at 2 y (7.6–16.2%) | HR 0.76 (95% CI 0.64–0.91)Updated analysis after the primary endpoint was met (data cut-off 25 February 2022). Median follow-up was 23.4 months (95% CI 20.6 to 25.2) in the durvalumab group and 22.4 months (21.4 to 23.8) in the placebo group; the result field shows the durvalumab-group value. Deaths: 248 (73%) and 279 (81%). No P value is given in the abstract. |
| OSFull analysis set (the abstract does not define it further) | long term-updatemedian follow-up 41.3 monthsOh 2025 | median 12.9 months (11.6–14.1); 14.6% at 3 y | median 11.3 months (10.1–12.5); 6.9% at 3 y | HR 0.74 (95% CI 0.63–0.87)The abstract calls these updated exploratory analyses. Median follow-up 41.3 months (95% CI 39.3 to 44.1) in all participants. The abstract gives no confidence intervals for the 36-month rates and no P value. |
| Endpoint | Analysis | Durvalumab plus gemcitabine and cisplatin | Placebo plus gemcitabine and cisplatin | Effect |
|---|---|---|---|---|
| OSRandomly assigned patients (the abstract does not name the analysis set) | primaryOh 2022 | 24.9% at 2 y (17.9–32.5%) | 10.4% at 2 y (4.7–18.8%) | HR 0.80 (95% CI 0.66–0.97)P=0.021Deaths at data cut-off: 198 (58.1%) with durvalumab and 226 (65.7%) with placebo. The abstract gives no medians; the later TOPAZ-1 paper (Lancet Gastroenterol Hepatol 2024) describes the primary result as a preplanned interim analysis. Medians for this analysis are in the label-based result below. |
| OSRandomized patients, N=341 and N=344 (FDA prescribing information) | primarySource 2026 | median 12.8 months (11.1–14.0) | median 11.5 months (10.1–12.5) | HR 0.80 (95% CI 0.66–0.97)P=0.021Same analysis as the primary report (198 and 226 deaths), as tabulated in the FDA prescribing information (section 14.3, Table 33): Kaplan-Meier median with 95% CI by the Brookmeyer-Crowley method; two-sided stratified log-rank P value against an alpha boundary of 0.030. These medians are from the label text, not from the journal abstract. |
| PFSRandomly assigned patients (the abstract does not name the analysis set) | primaryOh 2022 | — | — | HR 0.75 (95% CI 0.63–0.89)P=0.001Secondary end point. The abstract gives no median progression-free survival. |
| ORRRandomly assigned patients (the abstract does not name the analysis set) | primaryOh 2022 | 26.7% | 18.7% | Secondary end point; the abstract gives no confidence intervals or P value for the objective response rates. |
| OSFull analysis set (all randomly assigned participants) | long term-updatemedian follow-up 23.4 monthsOh 2024 | median 12.9 months (11.6–14.1); 23.6% at 2 y (18.7–28.9%) | median 11.3 months (10.1–12.5); 11.5% at 2 y (7.6–16.2%) | HR 0.76 (95% CI 0.64–0.91)Updated analysis after the primary endpoint was met (data cut-off 25 February 2022). Median follow-up was 23.4 months (95% CI 20.6 to 25.2) in the durvalumab group and 22.4 months (21.4 to 23.8) in the placebo group; the result field shows the durvalumab-group value. Deaths: 248 (73%) and 279 (81%). No P value is given in the abstract. |
| OSFull analysis set (the abstract does not define it further) | long term-updatemedian follow-up 41.3 monthsOh 2025 | median 12.9 months (11.6–14.1); 14.6% at 3 y | median 11.3 months (10.1–12.5); 6.9% at 3 y | HR 0.74 (95% CI 0.63–0.87)The abstract calls these updated exploratory analyses. Median follow-up 41.3 months (95% CI 39.3 to 44.1) in all participants. The abstract gives no confidence intervals for the 36-month rates and no P value. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.8 | 0.66–0.97 |
| OS | 0.8 | 0.66–0.97 |
| PFS | 0.75 | 0.63–0.89 |
| OS | 0.76 | 0.64–0.91 |
| OS | 0.74 | 0.63–0.87 |
- Durvalumab plus gemcitabine and cisplatin (experimental)
- Placebo plus gemcitabine and cisplatin (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Durvalumab plus gemcitabine and cisplatin | Placebo plus gemcitabine and cisplatin |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 8 | 64.8% | 61.7% |
| 16 | 42.0% | 38.1% |
| 24 | 27.3% | 23.5% |
| 32 | 17.7% | 14.5% |
- Durvalumab plus gemcitabine and cisplatin (experimental)
- Placebo plus gemcitabine and cisplatin (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Durvalumab plus gemcitabine and cisplatin | Placebo plus gemcitabine and cisplatin |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 8 | 65.1% | 61.2% |
| 16 | 42.3% | 37.5% |
| 24 | 27.5% | 22.9% |
| 32 | 17.9% | 14.0% |
Appears in
Sources
Oh DY, Ruth He A, Qin S, Chen LT, Okusaka T, Vogel A, et al. Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer. NEJM Evid. 2022;1(8):EVIDoa2200015.
FDA. Prescribing information, Imfinzi (durvalumab), label version effective 31 August 2026 (openFDA drug label record, set ID 8baba4ea-2855-42fa-9bd9-5a7548d4cec3).
Oh DY, He AR, Bouattour M, Okusaka T, Qin S, Chen LT, et al. Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): updated overall survival from a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024;9(8):694-704.
Oh DY, He AR, Qin S, Chen LT, Okusaka T, Kim JW, et al. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study. J Hepatol. 2025;83(5):1092-1101.