Background
Phase III RCT of 723 patients with metastatic RCC who progressed on one prior first-line therapy (sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines).
Interventions and follow up
Arm A: Axitinib 5mg PO BID
Arm B: Sorafenib 400mg PO BID
Primary endpoint: PFS
Arm B: Sorafenib 400mg PO BID
Primary endpoint: PFS
Results
mPFS (A vs B): 6.7mo vs 4.7mo, HR 0.665, 95%CI 0.544-0.812, one-sided P<.0001
mPFS, prior-sunitinib subgroup: 4.8mo vs 3.4mo
mPFS, prior-cytokine subgroup: 12.1mo vs 6.5mo
mOS (A vs B): 20.1mo vs 19.2mo, HR 0.969, 95%CI 0.800-1.174, one-sided P=.3744
mPFS, prior-sunitinib subgroup: 4.8mo vs 3.4mo
mPFS, prior-cytokine subgroup: 12.1mo vs 6.5mo
mOS (A vs B): 20.1mo vs 19.2mo, HR 0.969, 95%CI 0.800-1.174, one-sided P=.3744
Adverse events
Discontinuation due to AEs (A vs B): 4% vs 8%
Common toxicities: arm A — diarrhea, fatigue, hypertension; arm B — diarrhea, hand-foot syndrome, alopecia
Common toxicities: arm A — diarrhea, fatigue, hypertension; arm B — diarrhea, hand-foot syndrome, alopecia
Conclusions
Axitinib improved PFS versus sorafenib in the second-line setting for metastatic RCC, without an OS benefit.
Key Limitations
Open-label design; sorafenib comparator now considered a weaker control; no OS benefit; predates the IO era, so findings have limited relevance to modern second-line sequencing after IO-based first-line therapy.
Clinical Context
FDA approved axitinib (2012) for advanced RCC after failure of one prior systemic therapy. ESMO guidelines historically endorsed axitinib as a second-line VEGFR-TKI option; current sequencing after IO-based first-line favors cabozantinib or other agents.