CheckMate 214 trial

Background

Phase III RCT (N=1,096) of treatment-naive inoperable, locally advanced or metastatic clear-cell RCC (IMDC favorable 23%, intermediate 61%, poor 17%).

Interventions and follow up

Arm A: Nivolumab 3mg/kg + ipilimumab 1mg/kg IV q3wk x4 doses, then nivolumab 3mg/kg q2wk
Arm B: Sunitinib 50mg/d 4wk on / 2wk off
Primary endpoints: OS, PFS, and ORR in IMDC intermediate/poor-risk patients
Median follow-up: 55mo

Results

OS, entire population (A vs B): mOS not reached vs 38.4mo; 4-yr OS 53.4% vs 43.3%; HR 0.69, 95% CI 0.59-0.81
OS, int/poor risk: mOS 48.1mo vs 26.6mo; 4-yr OS 50.0% vs 35.8%; HR 0.65, 95% CI 0.54-0.78
OS, favorable risk: 4-yr OS 65.1% vs 68.9%; HR 0.93, 95% CI 0.62-1.40
PFS, int/poor risk: mPFS 11.2mo vs 8.3mo; 4-yr PFS 32.7% vs 12.3%; HR 0.74, 95% CI 0.62-0.88
PFS, favorable risk: 4-yr PFS 25.4% vs 31.6%; HR 1.84, 95% CI 1.29-2.62
ORR (entire population): 42% vs 27%

Adverse events

Grade 3-4 treatment-related AEs (A vs B): 46% vs 63%
Discontinuation due to AEs (A vs B): 22% vs 12%; immune-mediated toxicities required glucocorticoids in a substantial fraction of arm A

Conclusions

Nivolumab plus ipilimumab significantly improved OS, PFS, and ORR versus sunitinib in IMDC intermediate/poor-risk metastatic clear-cell RCC, with durable benefit. No benefit in favorable-risk patients.

Key Limitations

Benefit limited to intermediate/poor-risk group; favorable-risk PFS favored sunitinib; immune-related toxicity requiring steroids; clear-cell histology only.

Clinical Context

FDA approved nivolumab/ipilimumab (Apr 2018) for intermediate/poor-risk advanced RCC. A preferred first-line IO-IO regimen for intermediate/poor-risk disease per ASCO/ESMO, offering treatment-free survival; not preferred for favorable-risk disease.

References