CASPIAN
Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer
Phase 3N = 805NCT03043872
- Population
- Adults with treatment-naive extensive-stage small-cell lung cancer, WHO performance status 0 or 1, measurable disease
- Design
- Randomised (1:1:1) phase 3 trial at 209 sites in 23 countries: durvalumab plus platinum-etoposide, durvalumab plus tremelimumab plus platinum-etoposide, or platinum-etoposide alone. Platinum-etoposide used etoposide 80-100 mg/m2 days 1-3 with investigator's choice of carboplatin or cisplatin. The 2019 report was open-label; the 2021 update describes the trial as open-label and sponsor-blind. The primary endpoint was OS in the ITT population; the 2019 paper reports a planned interim analysis of durvalumab plus platinum-etoposide versus platinum-etoposide. The registry lists 987 enrolled; the papers randomised 805.
- Primary endpoint
- OS
- Arms
- Durvalumab plus platinum-etoposide (experimental, n = 268): Durvalumab 1500 mg plus platinum-etoposide every 3 weeks for up to four cycles, then durvalumab 1500 mg every 4 weeks
- Durvalumab plus tremelimumab plus platinum-etoposide (experimental, n = 268): Durvalumab 1500 mg plus tremelimumab 75 mg plus platinum-etoposide every 3 weeks for up to four cycles, then durvalumab 1500 mg every 4 weeks
- Platinum-etoposide (control, n = 269): Platinum-etoposide every 3 weeks for up to six cycles, with optional prophylactic cranial irradiation at the investigator's discretion
- People
- Paz-Ares L, CASPIAN investigators
OSHR 0.73 (95% CI 0.59–0.91)Δ median OS+2.7 monthsΔ 18-month OS+9 pointsOSHR 0.75 (95% CI 0.62–0.91)Δ median OS+2.4 monthsOSHR 0.82 (95% CI 0.68–1.00)
Show the numbers
| Endpoint | Analysis | Durvalumab plus platinum-etoposide / Durvalumab plus tremelimumab plus platinum-etoposide | Platinum-etoposide | Effect |
|---|---|---|---|---|
| OS | interimPaz-Ares 2019 | median 13 months (11.5–14.8); 34% at 18 mo (26.9–41.0%) | median 10.3 months (9.3–11.2); 25% at 18 mo (18.4–31.6%) | HR 0.73 (95% CI 0.59–0.91)P=0.0047Durvalumab plus platinum-etoposide versus platinum-etoposide only; the durvalumab plus tremelimumab arm was not reported in this paper. Landmark figures are the percentage alive at 18 months. |
| OS | long term-updatemedian follow-up 25.1 monthsGoldman 2021 | median 12.9 months (11.3–14.7) | median 10.5 months (9.3–11.2) | HR 0.75 (95% CI 0.62–0.91)P=0.0032Updated analysis. The abstract labels the p value 'nominal'. |
| OS | primarymedian follow-up 25.1 monthsGoldman 2021 | median 10.4 months (9.6–12.0) | median 10.5 months (9.3–11.2) | HR 0.82 (95% CI 0.68–1.00)P=0.045The abstract states this arm was not associated with a significant improvement in OS versus platinum-etoposide; it is the primary analysis for this comparison. |
| Endpoint | Analysis | Durvalumab plus platinum-etoposide / Durvalumab plus tremelimumab plus platinum-etoposide | Platinum-etoposide | Effect |
|---|---|---|---|---|
| OS | interimPaz-Ares 2019 | median 13 months (11.5–14.8); 34% at 18 mo (26.9–41.0%) | median 10.3 months (9.3–11.2); 25% at 18 mo (18.4–31.6%) | HR 0.73 (95% CI 0.59–0.91)P=0.0047Durvalumab plus platinum-etoposide versus platinum-etoposide only; the durvalumab plus tremelimumab arm was not reported in this paper. Landmark figures are the percentage alive at 18 months. |
| OS | long term-updatemedian follow-up 25.1 monthsGoldman 2021 | median 12.9 months (11.3–14.7) | median 10.5 months (9.3–11.2) | HR 0.75 (95% CI 0.62–0.91)P=0.0032Updated analysis. The abstract labels the p value 'nominal'. |
| OS | primarymedian follow-up 25.1 monthsGoldman 2021 | median 10.4 months (9.6–12.0) | median 10.5 months (9.3–11.2) | HR 0.82 (95% CI 0.68–1.00)P=0.045The abstract states this arm was not associated with a significant improvement in OS versus platinum-etoposide; it is the primary analysis for this comparison. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.73 | 0.59–0.91 |
| OS | 0.75 | 0.62–0.91 |
| OS | 0.82 | 0.68–1 |
- Durvalumab plus platinum-etoposide (experimental)
- Platinum-etoposide (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 platinum-etoposide | Platinum-etoposide |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 8 | 65.3% | 58.4% |
| 16 | 42.6% | 34.1% |
| 24 | 27.8% | 19.9% |
| 33 | 17.2% | 10.9% |
- Durvalumab plus platinum-etoposide (experimental)
- Platinum-etoposide (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 platinum-etoposide | Platinum-etoposide |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 8 | 65.1% | 59.0% |
| 16 | 42.3% | 34.8% |
| 24 | 27.5% | 20.5% |
| 32 | 17.9% | 12.1% |
Appears in
Sources
Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939.
Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):51-65.