Background
Phase II RCT (Alliance A031203) of 157 patients with treatment-naïve metastatic RCC of intermediate or poor IMDC risk (intermediate 80.9%, poor 19.1%).
Interventions and follow up
Arm A: Cabozantinib 60mg PO daily
Arm B: Sunitinib 50mg 4wk on, 2wk off
Primary endpoint: PFS
Arm B: Sunitinib 50mg 4wk on, 2wk off
Primary endpoint: PFS
Results
mPFS (A vs B): 8.2mo vs 5.6mo, HR 0.66, 95%CI 0.46-0.95, P=.012
mOS (A vs B): 30.3mo vs 21.8mo, HR 0.80, 95%CI 0.50-1.26
ORR (A vs B): 33% vs 12%
mOS (A vs B): 30.3mo vs 21.8mo, HR 0.80, 95%CI 0.50-1.26
ORR (A vs B): 33% vs 12%
Adverse events
Grade 3-4 overall (A vs B): 67% vs 69%
Selected grade 3-4 (A vs B): hypertension 28% vs 22%, fatigue 6% vs 15%, diarrhea 10% vs 11%, palmar-plantar erythrodysesthesia 8% vs 4%, cytopenias 3% vs 22%
Selected grade 3-4 (A vs B): hypertension 28% vs 22%, fatigue 6% vs 15%, diarrhea 10% vs 11%, palmar-plantar erythrodysesthesia 8% vs 4%, cytopenias 3% vs 22%
Conclusions
First-line cabozantinib improved PFS and ORR versus sunitinib in intermediate/poor-risk metastatic RCC; the OS difference was not statistically significant.
Key Limitations
Phase II, open-label, modest sample size; restricted to intermediate/poor-risk disease; OS underpowered and not significant; sunitinib monotherapy comparator superseded by IO-based first-line standards.
Clinical Context
Supported FDA expansion of cabozantinib to first-line advanced RCC (2017). ESMO recognizes single-agent cabozantinib as an option for intermediate/poor-risk patients unsuitable for IO-based combinations.