Background
Phase 3 non-inferiority RCT; N=1110 treatment-naive advanced/metastatic clear-cell renal cell carcinoma; pazopanib vs sunitinib, first line.
Interventions and follow up
Arm A: Pazopanib 800 mg PO daily (n=557)
Arm B: Sunitinib 50 mg PO daily, 4 wk on / 2 wk off (n=553)
Primary endpoint: Progression-free survival (non-inferiority)
Secondary: OS, safety, quality of life
Arm B: Sunitinib 50 mg PO daily, 4 wk on / 2 wk off (n=553)
Primary endpoint: Progression-free survival (non-inferiority)
Secondary: OS, safety, quality of life
Results
mPFS: 8.4 mo vs 9.5 mo, HR 1.05, 95% CI 0.90–1.22 (non-inferiority met).
mOS: no significant difference, HR 0.91, 95% CI 0.76–1.08.
mOS: no significant difference, HR 0.91, 95% CI 0.76–1.08.
Adverse events
Higher with sunitinib (G3–4): fatigue, hand-foot syndrome, leukopenia, thrombocytopenia, neutropenia.
Higher with pazopanib: elevated ALT/AST and bilirubin (hepatotoxicity).
Higher with pazopanib: elevated ALT/AST and bilirubin (hepatotoxicity).
Conclusions
Pazopanib was non-inferior to sunitinib for PFS and OS in first-line metastatic clear-cell RCC, with a more favorable safety and quality-of-life profile.
Key Limitations
Non-inferiority design (not superiority); QoL endpoints open to interpretation; pre-immunotherapy era — both single-agent VEGF TKIs have since been superseded by IO-based combinations in first-line RCC; clear-cell only.
Clinical Context
Pazopanib and sunitinib are both FDA/EMA approved for advanced RCC; COMPARZ established interchangeable efficacy and pazopanib's better tolerability. ESMO/ASCO now favor immunotherapy-based combinations (IO+IO or IO+TKI) first line; single-agent TKIs are reserved for selected patients with contraindications to IO.