Table 1.
Clinical trials of efficacy of everolimus in clear cell renal cell carcinoma
| Clinical trial | Arms | Design | Population | n | Median PFS (months) | ORR | Median OS (months) |
|---|---|---|---|---|---|---|---|
| Motzer et al46 | Everolimus vs placebo | Phase III randomized | Those with mRCC who progressed after one or more prior TKIs | Overall: 416 | Overall: 4.9 (everolimus) vs 1.9 (placebo) | 2% (everolimus) vs 0% (placebo) | Overall: 14.8 (everolimus) vs 14.4 (placebo) |
| RECORD-1 updated results | One previous TKI: 308 (184 sunitinib, 124 sorafenib) | After one TKI: 5.4 (everolimus) vs 1.9 (placebo) | Survival corrected for crossover was 1.9-fold longer with everolimus | ||||
| Two previous TKIs: 108 | After two TKIs: 4.0 (everolimus) vs 1.8 (placebo) | ||||||
| Pure second line after sunitinib: 56 | After sunitinib (as only previous therapy): 4.6 (everolimus) vs 1.8 (placebo) | ||||||
| Amato et al48 | Everolimus | Phase II | Those with mRCC who received one or no prior therapy | 41 | 11.2 (everolimus) | 14% (everolimus) | 22.1 (everolimus) |
| Hainsworth et al66 | BEV/EVE in first line vs second line | Phase II randomized | Those with mRCC who had received no prior systemic therapy or had progressed to sunitinib, sorafenib, or both | Overall: 80 Previously untreated: 50 Previously treated: 30 |
9.1 (BEV/EVE in first line) 7.1 (BEV/EVE in second line) |
30% (BEV/EVE in first line) 23% (BEV/EVE in second line) |
21.3 (BEV/EVE in first line) 15.5 (BEV/EVE in second line) |
| Motzer et al63 | Everolimus → sunitinib vs | Phase II randomized | Those with mRCC who had received no prior systemic therapy | Overall: 471 | PFS 1: 7.9 (everolimus → sunitinib) vs 10.7 (sunitinib → everolimus) | 8% (everolimus → sunitinib) vs 27% (sunitinib → everolimus) | 22.4 (everolimus → sunitinib) vs 32.0 (sunitinib → everolimus) |
| RECORD-3 | sunitinib → everolimus | 53.7% and 51.6% of patients who progressed to everolimus and sunitinib, respectively, received second line within the clinical trial | Combined PFS 1+2: 21.1 (everolimus → sunitinib) vs 25.8 (sunitinib → everolimus) | ||||
| Ravaud et al67 RECORD-2 |
EVE/BEV vs IFN/BEV | Phase II randomized | Those with mRCC who had received no prior systemic therapy | 365 | 9.3 (EVE/BEV) vs 10.0 (IFN/BEV) | 27% (EVE/BEV) vs 28% (IFN/BEV) | 27.1 (EVE/BEV) vs 27.1 (IFN/BEV) |
| Motzer et al69 RECORD-4 |
Everolimus | Phase II | Those with mRCC who progressed after one prior therapy | Overall: 134 | Overall: 7.8 (everolimus) | 7% (everolimus) | Overall: 23.8 (everolimus) |
| After sunitinib: 58 | After sunitinib: 5.7 (everolimus) | After sunitinib: 23.8 (everolimus) | |||||
| After other VEGF therapy: 62 | After other VEGF therapy: 7.8 (everolimus) | After other VEGF therapy: 17.2 (everolimus) | |||||
| After cytokines: 14 | After cytokines: 12.9 (everolimus) | After cytokines: NE | |||||
| Choueiri et al54 METEOR |
Cabozantinib vseverolimus | Phase III | Those with mRCC who progressed after one or more prior TKIs | 658 | 7.4 (cabozantinib) vs 3.9 (everolimus) | 17% (cabozantinib) vs 3% (everolimus) | 21.4 (cabozantinib) vs 16.5 (everolimus) |
| Motzer et al69 | Lenvatinib pluseverolimus vs lenvatinib vs everolimus | Phase II | Those with mRCC who progressed afterone prior TKI | 151 | Lenvatinib plus everolimus: 14.6 | Lenvatinib plus everolimus: 43% | Lenvatinib plus everolimus: 25.5 |
| Lenvatinib alone: 7.4 | Lenvatinib alone: 27% | Lenvatinib alone: 18.4 | |||||
| Everolimus alone: 5.5 | Everolimus alone: 6% | Everolimus alone: 17.5 | |||||
| Motzer et al53 CheckMate 025 |
Nivolumab vs everolimus | Phase III randomized | Those with mRCC who progressed after one or two prior antiangiogenic therapies | 821 One previous antiangiogenic therapy: 591 Two previous antiangiogenic therapies: 230 |
4.6 (nivolumab) vs 4.4 (everolimus) | 25% (nivolumab) vs 5% (everolimus) | 25.0 (nivolumab) vs 19.6 (everolimus) |
Abbreviations: PFS, progression-free survival; ORR, objective response rate; OS, overall survival; mRCC, metastatic renal cell cancer; TKI, tyrosine kinase inhibitor; BEV/EVE, bevacizumab/everolimus; IFN/BEV, interferon-α/bevacizumab; NE, not estimable.