Table 1.
Summary of key phase III trials in the use of immune checkpoint inhibitors in first-line treatment of metastatic RCC.
| Phase III Trial | Intervention | Control | Histology | Objective response rate | Progression Free Survival | Overall Survival |
|---|---|---|---|---|---|---|
| CheckMate 214, 2018 (15, 16) | Nivolumab (3mg/kg) & ipilimumab 1mg/kg) followed by nivolumab 3mg/kg every 2 weeks | Sunitinib 50mg daily for 4 weeks on, 2 weeks off | Clear cell |
Fav IMDC risk: 29.6 vs. 51.6% p=0.0005 Intermediate & poor IMDC risk: 41.9 vs. 26.8% p<0.0001 ITT: 39.1 vs. 32.4 p=0.0134 |
Fav IMDC risk: 12.4 vs. 28.9 months HR 1.84 95% CI (1.29-2.62) Intermediate & poor IMDC risk: 11.2 vs. 8.3 months HR 0.74 95% CI (0.62-0.88) ITT: 12.2 vs 12.3 months HR 0.89 95% CI (0.76-1.05) |
Fav IMDC risk: HR 0.93 95% CI 0.62-1.4 OS not reached Intermediate & poor IMDC risk: 48.1 vs. 26.6 months 50% vs. 35.8% HR 0.65 95% CI (0.54-0.78) ITT: 46.7 vs. 38.4 months 53.4% vs. 43.3% HR 0.69 95% CI (0.59-0.81) |
| JAVELIN Renal 101, March 2019 (17, 18) | Avelumab (10mg/kg) & axitinib 5mg twice daily | Sunitinib 50mg daily for 4 weeks on, 2 weeks off | Clear cell | 51.4% vs. 25.7% p value not available |
13.3 vs. 8.0 months p<0.0001 |
HR 0.796 95% CI 0.616-1.027 p=0.0392 (did not reach pre-specified significance level) |
| KEYNOTE-426, March 2019 (19, 20) | Pembrolizumab 200mg & axitinib 5mg twice daily | Sunitinib 50mg daily for 4 weeks on, 2 weeks off | Clear cell | 59.3% vs. 35.7% p< 0.001 |
15.4 vs. 11.1 months p<0.0001 |
HR 0.68 95% CI 0.55-0.85 p=0.0003 Median OS not reached |
| IMmotion151, May 2019 (21) | Atezolizumab 1200mg & bevacizumab 15mg/kg | Sunitinib 50mg daily for 4 weeks on, 2 weeks off | Clear cell Sarcomatoid allowed |
43% vs. 25% p value not available |
11.2 vs. 8.4 months p=0.0219 |
63% vs. 60% at 24 months p=0.4751 |
| CheckMate-9ER 2020 (22) | Nivolumab 240mg & cabozantinib 40mg daily | Sunitinib 50mg daily for 4 weeks on, 2 weeks off | Clear cell Sarcomatoid allowed | 55.7% vs. 27.1% p<0.0001 |
16.6 vs. 8.3 months HR 0.51 95% CI 0.41-0.64 p<0.0001 |
85.7% vs. 75.6% at 12 months HR 0.6, 98% CI 0.4-0.89 P=0.001 |
| CLEAR, 2021 (23) |
Arm A: lenvatinib & pembrolizumab Arm B: lenvatinib & everolimus |
Sunitinib 50mg daily for 4 weeks on, 2 weeks off | Clear cell Sarcomatoid allowed |
71% vs. 53.5% vs. 36.1% p value not available |
Arm A vs. control: 23.9 vs. 9.2 months p<0.001 Arm B vs. control: 14.7 vs. 9.2 months p <0.01 |
Arm A vs. control: HR 0.66 95% CI 0.49-0.88 p=0.005 OS not reached Arm B vs. control: HR 1.15 95% CI 0.88-1.5 p=0.3 OS not reached |