Table 2 Major clinical trials for the treatment of mRCC after anti-angiogenesis therapy
From: New treatment options for metastatic renal cell carcinoma with prior anti-angiogenesis therapy
Study | Everolimus | Axitinib | Sorafenib | Cabozantinib | Nivolumab | Lenvatinib/everolimus |
|---|---|---|---|---|---|---|
Record-1 | Axis | Intorsect | Meteor | Checkmate 025 | NCT01136733 (phase II) | |
Control | Placebo | Sorafenib | Temsirolimus | Everolimus | Everolimus | Everolimus |
Population | Metastatic RCC progressive on sunitinib, sorafenib, or both | Metastatic RCC progressive on either sunitinib, bevacizumab/IFNα, temsirolimus, or cytokine-based regimen (only 1 line of treatment allowed) | Metastatic RCC progressive on sunitinib | Metastatic RCC progressive on at least one VEGFR-targeting inhibitor but no limit on the number of lines of prior treatment | Metastatic RCC progressive on one or two anti-angiogenic therapy | Metastatic RCC progressive on one line of VEGF-directed therapy |
Crossover allowed? | Yes | No | Not specified | No | Not specified | Not specified |
1° endpoint | PFS 4.9 months (everolimus) vs. 1.9 months (placebo) | PFS 8.3 months (axitinib) vs. 5.7 months (everolimus) | PFS 3.9 months (sorafenib) vs. 4.3 months (temsirolimus) | PFS 7.4 months (cabozantinib) vs. 3.8 months (everolimus) | OS 25 months (nivolumab) vs. 19.6 months (everolimus) | PFS 14.6 months (lenvatinib/everolimus) vs. 5.5 months (everolimus) |
2° endpoints |  | |||||
OS | 14.8Â months (everolimus) vs. 14.4Â months (placebo) | 20.1Â months (axitinib) vs. 19.2Â months (everolimus) | 16.6Â months (sorafenib) vs. 12.3Â months (temsirolimus) | 21.4Â months (cabozantinib) vs. 16.5Â months (everolimus) | See above | 25.5Â months (lenvatinib/everolimus) vs. 17.5Â months (everolimus) |
ORR | 1.5% (everolimus) vs. 0% (placebo) | 19% (axitinib) vs. 9% (everolimus) | 8% in both arms | 21% (cabozantinib) vs. 5% (everolimus) | 25% (nivolumab) vs. 5% (everolimus) | 43% (lenvatinib/everolimus) vs. 6% (everolimus) |
PFS | See above | See above | See above | See above | 4.6Â months (nivolumab) vs. 4.4Â months (everolimus) | See above |
Median time to response | Not provided | Not provided | Not provided | Not provided | 3.5Â months (nivolumab) vs. 3.7Â months (everolimus) | Not provided |
Duration of response | Not provided | 11Â months (axitinib) vs. 10.6Â months (everolimus) | Not provided | Not provided | 12Â months for both arms | 13Â months (lenvatinib/everolimus) vs. 8.5Â months (everolimus) |
Discontinuation rate for toxicity | 10% (everolimus) vs. 4% (placebo) | 4% (axitinib) vs. 8% (everolimus) | Not provided | 9% (cabozantinib) vs. 10% (everolimus) | 8% (nivolumab) vs. 13% (everolimus) | Not provided |
Grade 3–4 toxicity | Everolimus: stomatitis (3%), infections (3%), pneumonitis (3%) | Axitinib: hypertension (16%), diarrhea (11%), fatigue (11%) | Sorafenib: palmar-plantar erythrodysesthesia (15%), rash (3%), and fatigue (7%) | Cabozantinib: hypertension (15%), diarrhea (11%), fatigue (9%) | Nivolumab: fatigue (2%) | Lenvatinib/everolimus: diarrhea (20%) |