Background
Phase III RCT of 626 patients with treatment-naïve poor-risk metastatic RCC.
Interventions and follow up
Arm A: Temsirolimus 25mg IV q1wk
Arm B: Interferon-alfa up to 18 MU SC 3×/wk
Arm C: Temsirolimus 15mg weekly + interferon-alfa 6 MU 3×/wk
Primary endpoint: OS
Arm B: Interferon-alfa up to 18 MU SC 3×/wk
Arm C: Temsirolimus 15mg weekly + interferon-alfa 6 MU 3×/wk
Primary endpoint: OS
Results
mOS, arm A vs B: 10.9mo vs 7.3mo, HR 0.73, 95%CI 0.58-0.92, P=.008
mOS, arm C vs B: 8.4mo vs 7.3mo, HR 0.96, 95%CI 0.76-1.20, P=.70
mPFS (A vs B vs C): 3.8mo vs 1.9mo vs 3.7mo
ORR (A vs B vs C): 8.6% vs 4.8% vs 8.1%
mOS, arm C vs B: 8.4mo vs 7.3mo, HR 0.96, 95%CI 0.76-1.20, P=.70
mPFS (A vs B vs C): 3.8mo vs 1.9mo vs 3.7mo
ORR (A vs B vs C): 8.6% vs 4.8% vs 8.1%
Adverse events
Grade 3-4 with temsirolimus: asthenia (11%), anemia, dyspnea, hyperglycemia; stomatitis and rash common
Combination arm: higher toxicity than either monotherapy
Combination arm: higher toxicity than either monotherapy
Conclusions
Single-agent temsirolimus improved OS versus interferon-alfa in poor-risk metastatic RCC; the combination conferred no survival benefit and added toxicity.
Key Limitations
Open-label design; restricted to poor-risk patients, limiting generalizability; interferon comparator and the mTOR-inhibitor approach are now largely obsolete in the IO and VEGFR-TKI era.
Clinical Context
FDA approved temsirolimus (2007) for advanced RCC. Historically an option for poor-risk disease per ESMO; superseded by IO-based combinations, with mTOR inhibitors now reserved for later lines.
References