Table 1.
Presented phase III studies regarding combination immune checkpoint inhibitor and anti-angiogenic therapy trials in previously untreated, advanced-stage clear-cell renal cell carcinoma.
| Trial | Study Population | Drugs | Enrollment | Primary Outcome Measures | Key Outcomes |
|---|---|---|---|---|---|
| IMmotion151 [107] NCT02420821 |
Previously untreated, advanced RCC with clear-cell or sarcomatoid histology Any IMDC risk group |
Arm 1: Atezolizumab 1200 mg plus bevacizumab 15 mg/kg IV Q3W Arm 2: Sunitinib 50 mg PO daily, 4 weeks on treatment followed by 2 weeks off treatment |
915 | PFS in the PD-L1-positive population and OS in ITT population | mPFS in PDL1 + ve patients: atezolizumab + bevacizumab vs. sunitinib: 11.2 mo vs. 7.7 mo. HR 0.74; 95%CI 0.57–0.96; p = 0.0217 OS in ITT (interim): atezolizumab + bevacizumab vs. sunitinib: 43% vs. 42%. HR 0.93; 95%CI 0.76–1.14; p = 0.4751 |
| KEYNOTE-426 [4] NCT02853331 |
Previously untreated, advanced RCC with clear-cell component with or without sarcomatoid features Any IMDC risk group |
Arm 1: Pembrolizumab 200 mg IV Q3W and axitinib 5 mg PO twice daily Arm 2: Sunitinib 50 mg PO daily, 4 weeks on treatment followed by 2 weeks off treatment |
861 | PFS | mPFS: pembrolizumab + axitinib vs. sunitinib: 15.1 mo vs. 11.1 mo. HR 0.69; 95%CI 0.57–0.84; p < 0.001 |
| JAVELIN Renal 101 [108] NCT02684006 |
Previously untreated, advanced RCC with a clear-cell component |
Arm 1: Avelumab 10 mg/kg IV Q2W plus axitinib 5 mg PO BD Arm 2: Sunitinib 50 mg PO daily, 4 weeks on treatment followed by 2 weeks off treatment |
886 | PFS and OS in patients with PD-L1-positive tumors | 63.2% had PD-L1-positive tumors. mPFS in PD-L1-positive tumors: avelumab + axitinib vs. sunitinib: 13.8 mo vs. 7.2 mo. HR 0.61; 95%CI 0.47–0.79; p < 0.001. OS in PD-L1-positive tumors: avelumab + axitinib vs. sunitinib: HR 0.82; 95%CI 0.53–1.28; p = 0.38 |
| CLEAR [3] NCT02811861 |
Previously untreated, advanced RCC with a clear-cell component Any IMDC risk group |
Arm 1: Lenvatinib 18 mg PO daily plus everolimus 5 mg PO daily Arm 2: Lenvatinib 20 mg PO daily plus pembrolizumab 200 mg IV Q3W Arm 3: Sunitinib 50 mg PO daily, 4 weeks on treatment followed by 2 weeks off treatment |
1069 | PFS | Lenvatinib + pembrolizumab vs. sunitinib: 23.9 mo vs. 9.2 mo; HR 0.39; 95%CI 0.32–0.49; p < 0.001) Lenvatinib plus everolimus vs. sunitinib: 14.7 mo vs. 9.2 mo; HR 0.65; 95%CI 0.53–0.80; p < 0.001) |
| CheckMate 9ER [2] NCT03141177 |
Previously untreated, advanced RCC with a clear-cell component Any IMDC risk group |
Arm 1: Nivolumab 240 mg IV Q2W plus cabozantinib 40 mg PO daily Arm 2: Sunitinib 50 mg PO daily, 4 weeks on treatment followed by 2 weeks off treatment |
651 | PFS | Nivolumab + cabozantinib vs. sunitinib: 16.6 mo vs. 8.3 mo; HR 0.51; 95%CI 0.41–0.64; p < 0.001) |
Abbreviations: RCC = renal cell carcinoma; IMDC = international metastatic RCC database consortium; Q3W = every 3 weeks; PFS = progression-free survival; mPFS = median progression-free survival; PD-L1 = programmed cell death ligand-1; ITT = intention to treat; OS = overall survival; PO = per oral; IV = intravenous; 95%CI = 95% confidence interval; Q2W = every 2 weeks; HR = hazard ratio.