pembrolizumab plus axitinib (n=432) vs. sunitinib (n=429)
randomized controlled trial
pembrolizumab plus axitinib
pembrolizumab was administred at a dose of 200 mg once every 3 weeks. Axitinib was administered orally at a dose of 5 mg twice daily, the dose could be increased to 7 mg,then 10 mg, twice daily if safety criteria were met and reduced to 3 mg, then 2 mg, twice daily to manage toxic effects
sunitinib
Sunitinib was administered orally at a dose of 50 mg daily for the first 4 weeks of each 6-week cycle the dose could be reduced to 37.5 mg, then 25 mg, for the first 4 weeks of each 6-week cycle to manage toxic effects.
metastatic/advanced RCC (mRCC) - 1st line (L1)
First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma
open-label
129 sites in 16 countries
P3 / one-sided test procedure with TWO interim analysis. Repartition between coprimary endpoints, and hierarchy with ORR
Among patients with previously untreated advanced renal-cell carcinoma, treatmentwith pembrolizumab plus axitinib resulted in significantly longer overall survival andprogression-free survival, as well as a higher objective response rate, than treatmentwith sunitinib.
KEYNOTE-581/CLEAR (PDL1), 2021 NCT02811861
pembrolizumab plus lenvatinib (n=355) vs. sunitinib (n=357)
randomized controlled trial
lenvatinib plus pembrolizumab
LENVIMA (20 mg orally once daily) in combination with KEYTRUDA (200 mg intravenously every three weeks)
sunitinib
Sunitinib (50 mg orally once daily for four weeks on treatment, followed by two weeks off treatment)
3 arms : lenvatinib plus pembrolizumab, lenvatinib plus everolimus and sunitinib
metastatic/advanced RCC (mRCC) - 1st line (L1)
Karnofsky performance-status scoreof at least 70
open label
200 sites in 20 countries
P3/ two sided and two interim analysis. A sequential approach for multiple comparisons was used to adjust for multiplicity and to control the familywise error rate for progression-free survival and overall survival and the percentage of patients with an objective responseat the alpha of 0.0499 (two-sided) in comparisonsof each combination regimen with sunitinib.
The combination of pembrolizumab (Keytruda) plus lenvatinib (Lenvima) significantly improved progression-free survival (PFS), overall survival (OS), and the objective response rate (ORR) compared with sunitinib (Sutent) as first line in patient with advancedrenal cell carcinoma