Table 5.
Single drugs and combinations approved for metastatic CCRC.
| Trial | Authors | Endpoint | mOS HR (95% IC) |
mPFS HR (95% IC) |
ORR |
|---|---|---|---|---|---|
| Sunitinib vs. INF alfa | Motzer et al., 2009 [36] | Primary: PFS; ORR Secondary: OS |
26.4 ms vs. 21.8 HR 0.821; p = 0.051 |
11 vs. 5 months HR 0.42 p < 0.001 |
31% vs. 3% |
| Pazopanib vs. IL2 or INF alfa | Sternberg et al., 2010 [38] | Primary: PFS Secondary: OS, ORR |
No differences | 7.4 vs. 4.2 months HR 0.46 p < 0.0000001 |
30% vs. 3% |
| Cabozantinib vs. everolimus METEOR study |
Choueiri et al., 2016 [51] | Primary: PFS Secondary: OS; ORR |
No differences |
7.4 vs. 3.8 months HR 0.58 p < 0.0001 |
21% vs. 5% |
| Nivolumab plus cabozantinib vs. sunitinb |
Choueiri et al., 2020 [68] | Primary: PFS Secondary: OS; ORR |
Probability of OS at 12 months: 85.7% vs. 75.6% HR 0.60 p = 0.001 mOS not reached |
16.6 vs. 8.3 months HR 0.51 p < 0.001 |
55% vs. 27.1% |
| Pembrolizumab plus lenvatinib vs. lenvatinib plus everolimus or sunitinb | Motzer et al., 2021 [71] | Primary: PFS Secondary: OS; ORR |
mOS not reached; HR for death (lenv + pem vs. suni): 0.66 p = 0.005 |
23.9 vs. 9.2 months (sunitinb) and 14.7 (everolimus) HR 0.39 p < 0.001 |
71% vs. 53% vs. 36.1% |
| Pembrolizumab plus axitinib vs. sunitinib Keynote 426 |
Rini et al., 2019 [69] | Primary: OS; PFS Secondary: ORR; DOR; safaty |
NR vs. 35.7 HR 0.68 (0.55–0.85) p < 0.001 |
15.4 vs. 11.1 months HR 0.71 (0.60–0.84) p < 0.001 |
60% vs. 40% p < 0.0001 |
| Nivolumab plus ipilimumab vs. sunitinb | Motzer et al., 2018 [73] | Primary: OS; PFS; ORR Secondary: ORR; OS PFS in ITT population; safety |
NR vs. 26 months HR 0.63 p < 0.001 |
11.6 vs. 8.4 months HR 0.82 p = 0.03 |
42% vs. 27% |
| Bevacizumab + INF alfa vs. INFalfa + placebo Avoren study |
Escudier et al., 2007 [23] | Primary: PFS Secondary: ORR; OS |
No differences | 10.2 vs. 5.4 months HR 0.63 p = 0.0001 |
25% vs. 13% CALGB study |
| Sorafenib vs. placebo | Escudier et al., 2009 [45] | Primary: OS Secondary: PFS |
17.8 vs. 14.3 HR 0.78 p = 0.029 |
5.5 vs. 2.8 months HR 0.44 p < 0.00001 |
12% vs. 2% |
| Everolimus vs. placebo | Motzer et al., 2010 [56] | Primary: PFS Secondary: ORR; OS |
No differences | 4.9 vs. 1.9 months HR 0.55 p < 0.0001 |
1.8% vs. 0% |
| Temsirolimus vs. INF alfa Poor prognosis pz |
Hudes et al., 2007 [54] | Primary: PFS Secondary: ORR; OS |
10.9 vs. 7.3 months HR 0.73 p = 0.008 |
5.5 vs. 3.1 months HR 0.82 p < 0.0001 |
8.6% vs. 4.8% |
| Axitinib vs. sunitinb | Rini et al., 2011 [49] | Primary: PFS Secondary: ORR; OS |
No differences | 6.7 vs. 4.7 months HR 0.0665 p < 0.0001 |
8.6% vs. 4.8% |
| Atezolizumab + bevacizumab vs. sunitinib Phase II; ongoing phase III |
Atkins et al., 2019 [70] | Primary: PFS Secondary: ORR; OS |
Immature data |
14.7 vs. 8.4 months 11.2 vs. 7.7 in PDL1 positiveHR 0.64, p = 0.0095 |