ADRIATIC
Durvalumab, with or without tremelimumab, versus placebo after concurrent chemoradiotherapy in limited-stage small-cell lung cancer
Phase 3NCT03703297
- Population
- Patients with limited-stage small-cell lung cancer without disease progression after standard concurrent platinum-based chemoradiotherapy
- Design
- Double-blind, placebo-controlled phase 3 trial: durvalumab 1500 mg, durvalumab 1500 mg plus tremelimumab 75 mg (four doses only), or placebo every 4 weeks for up to 24 months; randomisation stratified by stage (I or II vs III) and receipt of prophylactic cranial irradiation. Co-primary endpoints OS and PFS (blinded independent central review, RECIST 1.1). Data are from the first planned interim analysis (cutoff 15 January 2024) of durvalumab versus placebo; results in the durvalumab-tremelimumab group remained blinded. The registry lists 730 enrolled.
- Primary endpoint
- OS, PFS
- Arms
- Durvalumab (experimental, n = 264): Durvalumab 1500 mg every 4 weeks for up to 24 months
- Durvalumab plus tremelimumab (experimental, n = 200): Durvalumab 1500 mg plus tremelimumab 75 mg (four doses only) every 4 weeks for up to 24 months
- Placebo (control, n = 266): Placebo every 4 weeks for up to 24 months
- People
- Cheng Y, ADRIATIC Investigators
OSHR 0.73Δ median OS+22.5 monthsPFSHR 0.76Δ median PFS+7.4 months
Show the numbers
| Endpoint | Analysis | Durvalumab / Durvalumab plus tremelimumab | Placebo | Effect |
|---|---|---|---|---|
| OSRandomised patients, durvalumab versus placebo | interimCheng 2024 | median 55.9 months | median 33.4 months (25.5–39.9) | HR 0.73P=0.01The hazard ratio is reported with a 98.321% CI of 0.54 to 0.98 (not a 95% CI). The 95% CI for the durvalumab median is 37.3 to not reached. First planned interim analysis. Grade 3 or 4 adverse events 24.4% with durvalumab and 24.2% with placebo; adverse events leading to discontinuation 16.4% and 10.6%; leading to death 2.7% and 1.9%; grade 3 or 4 pneumonitis or radiation pneumonitis 3.1% and 2.6%. |
| PFSRandomised patients, durvalumab versus placeboBlinded independent central review, RECIST 1.1 | interimCheng 2024 | median 16.6 months (10.2–28.2) | median 9.2 months (7.4–12.9) | HR 0.76P=0.02The hazard ratio is reported with a 97.195% CI of 0.59 to 0.98 (not a 95% CI). First planned interim analysis. |
| Endpoint | Analysis | Durvalumab / Durvalumab plus tremelimumab | Placebo | Effect |
|---|---|---|---|---|
| OSRandomised patients, durvalumab versus placebo | interimCheng 2024 | median 55.9 months | median 33.4 months (25.5–39.9) | HR 0.73P=0.01The hazard ratio is reported with a 98.321% CI of 0.54 to 0.98 (not a 95% CI). The 95% CI for the durvalumab median is 37.3 to not reached. First planned interim analysis. Grade 3 or 4 adverse events 24.4% with durvalumab and 24.2% with placebo; adverse events leading to discontinuation 16.4% and 10.6%; leading to death 2.7% and 1.9%; grade 3 or 4 pneumonitis or radiation pneumonitis 3.1% and 2.6%. |
| PFSRandomised patients, durvalumab versus placeboBlinded independent central review, RECIST 1.1 | interimCheng 2024 | median 16.6 months (10.2–28.2) | median 9.2 months (7.4–12.9) | HR 0.76P=0.02The hazard ratio is reported with a 97.195% CI of 0.59 to 0.98 (not a 95% CI). First planned interim analysis. |
- Durvalumab (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Durvalumab | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 35 | 64.8% | 48.4% |
| 70 | 42.0% | 23.4% |
| 105 | 27.2% | 11.3% |
| 140 | 17.6% | 5.5% |
- Durvalumab (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Durvalumab | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 10 | 65.9% | 47.1% |
| 21 | 41.6% | 20.6% |
| 31 | 27.4% | 9.7% |
| 42 | 17.3% | 4.2% |