Background
Phase III RCT of 658 patients with metastatic RCC previously treated with VEGFR-targeted therapy (VEGFR-TKI 71%; ≥2 prior therapies 29%; prior sunitinib 62%, pazopanib 43%, axitinib 16%).
Interventions and follow up
Arm A: Cabozantinib 60mg PO daily
Arm B: Everolimus 10mg PO daily
Primary endpoint: PFS
Median follow-up: ~18.8mo
Arm B: Everolimus 10mg PO daily
Primary endpoint: PFS
Median follow-up: ~18.8mo
Results
mPFS (A vs B): 7.4mo vs 3.9mo, HR 0.51, 95%CI 0.41-0.62, P<.0001
mOS (A vs B): 21.4mo vs 16.5mo, HR 0.66, 95%CI 0.53-0.83, P=.00026
ORR (A vs B): 21% vs 5%
mOS (A vs B): 21.4mo vs 16.5mo, HR 0.66, 95%CI 0.53-0.83, P=.00026
ORR (A vs B): 21% vs 5%
Adverse events
Dose reduction (A vs B): 60% vs 25%
Common grade 3-4 with cabozantinib: hypertension, diarrhea, fatigue, palmar-plantar erythrodysesthesia
Common grade 3-4 with cabozantinib: hypertension, diarrhea, fatigue, palmar-plantar erythrodysesthesia
Conclusions
Cabozantinib was superior to everolimus in PFS, OS, and ORR in previously treated metastatic RCC.
Key Limitations
Open-label design; everolimus comparator now considered weak; enrolled patients had prior VEGFR-TKI rather than IO-based therapy, so direct applicability to post-IO sequencing is inferential.
Clinical Context
FDA approved cabozantinib (2016) for advanced RCC after prior antiangiogenic therapy; EMA approval followed. ESMO guidelines list cabozantinib among preferred options for previously treated advanced RCC, including after IO-based regimens.