Background
Phase III open-label RCT (CASPIAN); N=805; treatment-naïve extensive-stage SCLC; randomized 1:1:1; updated 3-arm analysis at 25.1mo.
Interventions and follow up
Arm A: Durvalumab 1500mg + tremelimumab 75mg + platinum-etoposide, then maintenance durvalumab
Arm B: Durvalumab 1500mg + platinum-etoposide, then maintenance durvalumab
Arm C: Platinum-etoposide Q3W up to 6 cycles, optional prophylactic cranial irradiation
Primary endpoint: Overall survival
mFollow up: 25.1mo
Doses: etoposide 80-100mg/m2 D1-3; carboplatin AUC5-6 or cisplatin 75-80mg/m2 D1
Arm B: Durvalumab 1500mg + platinum-etoposide, then maintenance durvalumab
Arm C: Platinum-etoposide Q3W up to 6 cycles, optional prophylactic cranial irradiation
Primary endpoint: Overall survival
mFollow up: 25.1mo
Doses: etoposide 80-100mg/m2 D1-3; carboplatin AUC5-6 or cisplatin 75-80mg/m2 D1
Results
mOS, durva+treme vs chemo (A vs C): 10.4mo vs 10.5mo, HR 0.82, 95% CI 0.68-1.00, P=.045 (NS at boundary)
mOS, durva vs chemo (B vs C): 12.9mo vs 10.5mo, HR 0.75, 95% CI 0.62-0.91, P=.0032
mOS, durva vs chemo (B vs C): 12.9mo vs 10.5mo, HR 0.75, 95% CI 0.62-0.91, P=.0032
Adverse events
Hematologic (grade ≥3): Neutropenia 32% vs 24% vs 33% (A/B/C); anemia 13% vs 9% vs 18%
Immune-related (grade ≥3): 14% vs 5% vs <1%
Treatment-related deaths: 5% vs 2% vs 1%
Immune-related (grade ≥3): 14% vs 5% vs <1%
Treatment-related deaths: 5% vs 2% vs 1%
Conclusions
First-line durvalumab + platinum-etoposide improved OS vs chemotherapy in extensive-stage SCLC; adding tremelimumab did not significantly improve outcomes and increased toxicity.
Key Limitations
Open-label; chemo arm allowed cisplatin or carboplatin and PCI (immunotherapy arms did not), complicating comparison; no predictive biomarker; modest absolute OS benefit.
Clinical Context
FDA approved durvalumab + platinum-etoposide for first-line ES-SCLC (Mar 2020); EMA approved 2020. ESMO endorses durvalumab- or atezolizumab-based chemoimmunotherapy as first-line standard. Tremelimumab not added in this indication.