POSEIDON trial

Background

Phase 3 RCT (POSEIDON), 5-year analysis; N=761 metastatic NSCLC, any PD-L1, EGFR/ALK wild-type, first-line, comparing platinum chemo ± durvalumab ± tremelimumab.

Interventions and follow up

Arm A (T+D+CT): Tremelimumab 75 mg x1 dose + durvalumab 1500 mg IV q4w + 4 cycles platinum chemo, then durvalumab maintenance
Arm B (D+CT): Durvalumab + same chemo, no tremelimumab
Arm C (CT): Chemotherapy alone ± pemetrexed maintenance (non-squamous)
Primary endpoint: PFS (T+D+CT vs CT)
mFollow up: >5yr

Results

mPFS (T+D+CT vs CT): 6.2mo vs 4.8mo, HR 0.72, 95%CI 0.60-0.86, P<.001
mOS (T+D+CT vs CT): 14.0mo vs 11.7mo, HR 0.77, 95%CI 0.65-0.92, P=.003
mPFS (D+CT vs CT): 5.5mo vs 4.8mo, HR 0.74, 95%CI 0.62-0.89, P=.0009
mOS (D+CT vs CT): 13.3mo vs 11.7mo, HR 0.86, 95%CI 0.72-1.02, P=.075
ORR: 38% vs 41% vs 25.4%, T+D+CT vs D+CT vs CT

Adverse events

Overall: grade ≥3 AEs 51% (T+D+CT) vs 44% (CT)
Immune-related: any-grade irAEs 33% with T+D+CT (mostly thyroid disorders) vs 12% with CT

Conclusions

Adding limited-course tremelimumab to durvalumab + chemo produced durable long-term survival benefit, roughly doubling 5-year OS versus chemo, with manageable added immune toxicity.

Key Limitations

D+CT arm did not reach significant OS benefit; cross-trial comparisons to other chemo-IO regimens limited; added irAEs with the CTLA-4 component.

Clinical Context

FDA approved durvalumab + tremelimumab + chemo (1L metastatic NSCLC) November 2022; an option alongside other 1L chemo-immunotherapy regimens, with the long tail favoring the dual-IO arm.

References