Background
Phase III RCT (N=750) of treatment-naive metastatic clear-cell RCC.
Interventions and follow up
Arm A: Sunitinib 50mg/d 4wk on / 2wk off
Arm B: Interferon-alfa 9 MU SC 3x/week
Primary endpoint: PFS
Arm B: Interferon-alfa 9 MU SC 3x/week
Primary endpoint: PFS
Results
mPFS (A vs B): 11mo vs 5mo; HR 0.42, 95% CI 0.32-0.54, P<.001
ORR (A vs B): 31% vs 6%, P<.001
mOS (final analysis): 26.4mo vs 21.8mo; HR 0.82, 95% CI 0.67-1.00, P=.051
ORR (A vs B): 31% vs 6%, P<.001
mOS (final analysis): 26.4mo vs 21.8mo; HR 0.82, 95% CI 0.67-1.00, P=.051
Adverse events
Grade 3-4 with sunitinib: diarrhea (5%), vomiting, hypertension, hand-foot syndrome
Interferon arm: fatigue and asthenia more common; health-related quality of life favored sunitinib
Interferon arm: fatigue and asthenia more common; health-related quality of life favored sunitinib
Conclusions
Sunitinib markedly improved PFS, ORR, and quality of life versus interferon-alfa, establishing it as a first-line standard for metastatic clear-cell RCC.
Key Limitations
OS difference did not reach statistical significance, partly due to crossover; interferon comparator is no longer a relevant standard; clear-cell histology only.
Clinical Context
FDA approval of sunitinib for advanced RCC was supported by this trial; defined VEGFR TKI as first-line therapy for over a decade. Now largely replaced first-line by IO-TKI and IO-IO combinations per ASCO/ESMO, but sunitinib remains a common comparator and option.