Background
Randomized phase trial, N=221, in stage IB–IIIA resectable NSCLC. Patients were treatment-naive and eligible for surgical resection. This analysis evaluates the neoadjuvant nivolumab + ipilimumab arm vs chemotherapy.
Interventions and follow up
Arm A: Nivolumab 3 mg/kg IV Q2W for 3 cycles + ipilimumab 1 mg/kg IV once at cycle 1
Arm B: Platinum-doublet chemotherapy IV Q3W for 3 cycles
Primary endpoint: Event-free survival (EFS)
mFollow up: 49.2 mo
Arm B: Platinum-doublet chemotherapy IV Q3W for 3 cycles
Primary endpoint: Event-free survival (EFS)
mFollow up: 49.2 mo
Results
Definitive surgery: 73% vs 76%
Surgery canceled: 26% vs 19% (progression 16% vs 8%; AE 3% vs 0%; other 7% vs 11%)
Surgery delayed: 6% vs 11%
R0 resection: 80% vs 71%
EFS: 54.8 vs 20.9 mo, HR 0.77, 95% CI 0.51–1.15
OS: not reached vs not reached, HR 0.73, 95% CI 0.47–1.14
EFS by PD-L1 <1%: HR 1.32 (0.67–2.59)
EFS by PD-L1 ≥1%: HR 0.47 (0.25–0.88)
EFS by PD-L1 1–49%: HR 0.59 (0.29–1.21)
EFS by PD-L1 ≥50%: not computed
pCR: 20.4% vs 4.6%
ctDNA clearance: 11% vs 33%
Surgery canceled: 26% vs 19% (progression 16% vs 8%; AE 3% vs 0%; other 7% vs 11%)
Surgery delayed: 6% vs 11%
R0 resection: 80% vs 71%
EFS: 54.8 vs 20.9 mo, HR 0.77, 95% CI 0.51–1.15
OS: not reached vs not reached, HR 0.73, 95% CI 0.47–1.14
EFS by PD-L1 <1%: HR 1.32 (0.67–2.59)
EFS by PD-L1 ≥1%: HR 0.47 (0.25–0.88)
EFS by PD-L1 1–49%: HR 0.59 (0.29–1.21)
EFS by PD-L1 ≥50%: not computed
pCR: 20.4% vs 4.6%
ctDNA clearance: 11% vs 33%
Adverse events
Overall: Grade 3–4 treatment-related AE 14% (nivo+ipi) vs 36% (chemotherapy)
Surgical: Surgery canceled for AEs in 3% (nivo+ipi) vs 0% (chemotherapy)
Surgical: Surgery canceled for AEs in 3% (nivo+ipi) vs 0% (chemotherapy)
Conclusions
Neoadjuvant nivolumab + ipilimumab showed potential long-term benefit and higher pCR vs chemotherapy with fewer high-grade toxicities, though early progression and surgery cancellations were more frequent. Benefit was concentrated in PD-L1 ≥1% tumors, with no apparent benefit at PD-L1 <1% (HR 1.32).
Key Limitations
Small exploratory arm (N=221); EFS HR crossed 1 (95% CI 0.51–1.15); higher surgery cancellation in immunotherapy arm; PD-L1 ≥50% EFS not computed; OS immature.
Clinical Context
Neoadjuvant nivolumab + chemotherapy (CheckMate 816) is FDA/EMA approved and standard for resectable NSCLC; nivolumab + ipilimumab is not an established neoadjuvant regimen and remains investigational per ASCO/ESMO.