ADRIATIC trial

Background

Phase III, double-blind, placebo-controlled RCT (ADRIATIC). N=730 patients with limited-stage SCLC without progression after concurrent platinum-based chemoradiotherapy (cCRT). Prophylactic cranial irradiation (PCI) allowed (53.8% per arm). Three-arm design.

Interventions and follow up

Arm A: Durvalumab 1500 mg IV Q4W maintenance up to 24mo
Arm B: Durvalumab 1500 mg IV Q4W + tremelimumab 75 mg × 4 cycles → durvalumab maintenance up to 24mo (still blinded, future analysis)
Arm C: Placebo
Primary endpoint: OS and PFS (durvalumab vs placebo)
mFollow up: 37.2mo (OS), 27.6mo (PFS)

Results

OS: 55.9 vs 33.4mo, HR 0.73, 95% CI 0.57–0.93, P=.01
PFS: 16.6 vs 9.2mo, HR 0.76, 95% CI 0.61–0.95, P=.02
24mo OS: 68.0% vs 58.5%
36mo OS: 56.5% vs 47.6%

Adverse events

Pulmonary: pneumonitis/radiation pneumonitis 38.0% vs 30.2%, grade 3/4 in 3.0% vs 2.6%.
Overall: treatment discontinuation 16.3% vs 10.6%; treatment-related death 2.7% vs 1.9%. Safety consistent with known durvalumab profile.

Conclusions

Consolidation durvalumab after cCRT significantly improved OS and PFS vs placebo in limited-stage SCLC with acceptable tolerability, establishing a new standard of care in this setting.

Key Limitations

Durvalumab + tremelimumab arm remains blinded; combination value undefined. Optimal IO duration (24mo) not tested against shorter courses. Limited representation of patients receiving once-daily vs twice-daily thoracic RT regimens. No predictive biomarker. Pneumonitis incidence after cCRT warrants monitoring.

Clinical Context

FDA approved consolidation durvalumab (Dec 2024) for limited-stage SCLC not progressing after cCRT, the first IO approval in LS-SCLC and a practice change after decades without advances. ESMO endorses durvalumab consolidation in LS-SCLC after cCRT.

References