Background
Phase 3 RCT (CheckMate 73L), N=925, previously untreated unresectable stage III NSCLC amenable to CCRT with good PS. Compared nivolumab-based CCRT and consolidation (± ipilimumab) vs the PACIFIC regimen of CCRT + durvalumab consolidation.
Interventions and follow up
Arm A: Nivolumab + CCRT → consolidation nivolumab + ipilimumab.
Arm B: Nivolumab + CCRT → consolidation nivolumab alone.
Arm C (control): CCRT → consolidation durvalumab (PACIFIC regimen).
Primary endpoint: PFS, Arm A vs Arm C. Secondary: OS; PFS Arm B vs C; response; safety.
mFollow up: 30.5mo
Arm B: Nivolumab + CCRT → consolidation nivolumab alone.
Arm C (control): CCRT → consolidation durvalumab (PACIFIC regimen).
Primary endpoint: PFS, Arm A vs Arm C. Secondary: OS; PFS Arm B vs C; response; safety.
mFollow up: 30.5mo
Results
PFS, Arm A vs C (primary): HR 0.95, 96% CI 0.77–1.19, P=.65 — not met
OS, Arm A vs C (descriptive): HR 1.12, 95% CI 0.87–1.43 — no improvement
PFS, Arm B vs C: HR 0.84, 95% CI 0.69–1.04 — not improved
OS, Arm B vs C: HR 0.97, 95% CI 0.76–1.24 — not improved
OS, Arm A vs C (descriptive): HR 1.12, 95% CI 0.87–1.43 — no improvement
PFS, Arm B vs C: HR 0.84, 95% CI 0.69–1.04 — not improved
OS, Arm B vs C: HR 0.97, 95% CI 0.76–1.24 — not improved
Adverse events
Pulmonary: Both nivolumab-containing arms (A and B) had increased pneumonitis vs the durvalumab consolidation control.
Overall: Detailed grade ≥3 rates and treatment-related deaths NR in abstract.
Overall: Detailed grade ≥3 rates and treatment-related deaths NR in abstract.
Conclusions
Substituting nivolumab + CCRT followed by nivolumab ± ipilimumab consolidation for the PACIFIC regimen did not improve PFS or OS in unresectable stage III NSCLC and increased pneumonitis. Durvalumab consolidation after CCRT remains the standard of care.
Key Limitations
Negative primary endpoint with no signal in either experimental arm. Detailed safety (grade ≥3, treatment-related deaths) not fully reported. Open-label regimens. PD-L1 and histology subgroup interactions not established. Increased pneumonitis raises a tolerability concern for nivolumab + CCRT.
Clinical Context
CheckMate 73L reaffirms PACIFIC-regimen CCRT + durvalumab consolidation (FDA/EMA approved; ESMO-endorsed) as the standard for unresectable stage III NSCLC. No regulatory change for nivolumab in this setting. Sequencing of CCRT then durvalumab consolidation remains unchanged.