CheckMate 057

Background

Phase III, open-label RCT (CheckMate 057). N=582 with previously treated (≥1 prior platinum regimen) advanced non-squamous NSCLC, ECOG PS 0–1. No PD-L1 selection. Companion trial to CheckMate 017.

Interventions and follow up

Arm A: Nivolumab 3 mg/kg IV q2wk (N=292)
Arm B: Docetaxel 75 mg/m² IV q3wk (N=290)
Primary endpoint: Overall survival
mFollow up: 13.2 months

Results

OS: 12.2 vs 9.4 mo, HR 0.73 (95% CI 0.59–0.89), P=.002
1-yr OS: 51% vs 39%
PFS: curves crossed early (docetaxel initially superior, then nivolumab dominant)
ORR: 19% vs 12%
OS (PD-L1 ≥10%): HR 0.40 (0.27–0.59)
OS (PD-L1 <1%): HR 1.00 (no benefit)

Adverse events

Overall (grade ≥3): 10% (nivolumab) vs 54% (docetaxel)
Pulmonary: pneumonitis 3.4% (grade ≥3)
Endocrine: hypothyroidism 5.4% (all grades)

Conclusions

Nivolumab significantly improved OS vs docetaxel in previously treated non-squamous NSCLC (HR 0.73). Unlike CheckMate 017, PD-L1 predicted benefit — PD-L1 ≥10% OS HR 0.40, while PD-L1 <1% showed no benefit — underscoring biomarker importance in non-squamous NSCLC.

Key Limitations

PFS favored docetaxel initially (curves crossed), challenging it as an OS surrogate. No benefit in PD-L1 <1% subgroup (~35% of patients). Open-label design. EGFR/ALK-mutated patients were included without separate reporting at primary publication; these patients do not benefit from PD-1 inhibition. Post-progression salvage therapy not controlled.

Clinical Context

CheckMate 057 (non-squamous) with CheckMate 017 (squamous) established nivolumab as the first FDA-approved IO for 2L NSCLC (2015), dosed 3mg/kg q2wk (now standardized to 240mg q2wk or 480mg q4wk). The differential PD-L1 predictivity between histologies remains clinically relevant for biomarker-guided decisions. ESMO-MCBS 4.

References

Borghaei H et al, NEJM 2015 (primary OS) | Horn L et al, JCO 2018 (4-yr survival update)