Background
Phase III RCT (N=615) of resected locoregional clear-cell RCC at high risk of recurrence (stage III, pT3 or pN1, or greater), post-nephrectomy.
Interventions and follow up
Arm A: Sunitinib 50mg/d 4wk on / 2wk off x1yr
Arm B: Placebo
Primary endpoint: DFS by blinded independent central review
Median follow-up: 5.4yr (primary); ~6.6yr (updated analysis)
Arm B: Placebo
Primary endpoint: DFS by blinded independent central review
Median follow-up: 5.4yr (primary); ~6.6yr (updated analysis)
Results
mDFS by central review (A vs B): 6.8yr vs 5.6yr; HR 0.76, 95% CI 0.59-0.98, P=.03
mDFS by investigator (A vs B): 6.2yr vs 4.0yr; HR 0.74, 95% CI 0.55-0.99
mOS: not reached, data immature (no significant difference at analysis)
mDFS by investigator (A vs B): 6.2yr vs 4.0yr; HR 0.74, 95% CI 0.55-0.99
mOS: not reached, data immature (no significant difference at analysis)
Adverse events
Tolerability (A vs B): dose reduction 34.3% vs 2%; interruption 46.4% vs 13.2%; discontinuation 28.1% vs 5.6%
Most common sunitinib AEs: diarrhea 56.9%, hand-foot syndrome 50.3%, hypertension 38.6%, fatigue 36.6%, nausea 34.4%
Most common sunitinib AEs: diarrhea 56.9%, hand-foot syndrome 50.3%, hypertension 38.6%, fatigue 36.6%, nausea 34.4%
Conclusions
Adjuvant sunitinib x1yr significantly prolonged DFS versus placebo in high-risk locoregional clear-cell RCC.
Key Limitations
DFS benefit by central review only modest and not corroborated by an OS benefit; substantial toxicity and discontinuation; clear-cell, high-risk population only.
Clinical Context
FDA approved adjuvant sunitinib (Nov 2017) for high-risk RCC based on S-TRAC; EMA did not approve. Adoption was limited by lack of OS benefit and toxicity. Adjuvant pembrolizumab (KEYNOTE-564) is now the preferred adjuvant option per ASCO/ESMO.