Table 1:
Grouped histology.
| Agent (trial, year) | Phase | N per group | Histology (%) | Primary endpoint | ORR, % (95% CI) | mPFS, months (95% CI) |
OS, months (95% CI) |
|---|---|---|---|---|---|---|---|
| Sunitinib (2012)(17) | II | 31 | 22 (71) papillary 3 (10) chromophobe 5 (16) unclassified 1 (3) Xp11.2 translocation |
ORR | 35 (19–52) | 6.4 (4.2–8.6) | NR, estimated at 25.6 (8.4–42.9) 1-year OS: 65% |
| Sunitinib vs. everolimus (ESPEN, 2016)(18) |
II | 33 Sunitinib 35 Everolimus |
14 (43) papillary 6 (18) chromophobe 4 (12) unclassified 3 (9) translocation unspecified 6 (18) clear cell with sarcomatoid features 13 (38) papillary 6 (17) chromophobe 6 (17) unclassified 4 (11) translocation unspecified 6 (17) clear cell with sarcomatoid features |
PFS | 9 2.8 |
6.1 4.1 (P = 0.6) |
16.2 14.9 (P = 0.18) |
| Sunitinib vs. everolimus (ASPEN, 2016)(19) |
II | 51 Sunitinib 57 Everolimus |
33 (65) papillary 10 (20) chromophobe 8 (16) unclassified 37 (65) papillary 6 (10) chromophobe 14 (25) unclassified |
PFS | 18 9 |
8.3 (8.0–11.4) 5.6 (5.0–5.6) HR: 1.41 (0.03–1.92) |
31.5 (14.8–NA) 13.2 (9.7–37.9) HR: 1.12 (0.7–2.1) |
| Temsirolimus vs. sunitinib (CESAR, 2020)(20) | II | 12 Temsirolimus 10 Sunitinib |
8 (67) papillary 2 (17) chromophobe 1 (8) medullary 1 (8) unclassified 8 (80) papillary 2 (20) unclassified |
PFS | NA NA |
9.3 13.2 HR: 1.64 (0.65–4.18) |
19.4 19.8 |
| Pazopanib (2018)(22) |
II | 29 | 19 (66) papillary 3 (10) chromophobe 7 (24) unclassified |
ORR | 28 | 16.5 (10.9–22.1) | NR |
| Axitinib (2018)(23) | II | 40 | 26 (60) papillary 4 (10) chromophobe 7 (18) MiT translocation 3 (7) others |
PFS | 37.5 | 7.4 (5.2–9.5) | 12.1 (6.4–17.7) |
| Everolimus + bevacizumab (2016)(24) | II | 34 | 5 (14) papillary 5 (14) chromophobe 2 (6) medullary 23 (66) unclassified |
PFS | 29 | 11 (3.8–19.3) | 18.5 |
| Everolimus + bevacizumab (2020)(25) | II | 37 | 13 (35) papillary 1 (3) translocation unspecified 23 (62) unclassified |
PFS | 35 | 13.7 (10.8–16.4) | 33.9 (23.3–71.9) |
| Nivolumab (Checkmate 374, 2020)(26) |
IIIb/IV | 44 | 24 (55) papillary 7 (16) chromophobe 1 (2) medullary 1 (2) collecting duct 2 (5) translocation unspecified 8 (18) unclassified 1 (2) unreported |
High-grade immune-mediated adverse events | 13.6 (5.3–27.4) | 2.2 (1.8–5.4) | 16.3 (9.2–NE) |
| Atezolizumab + bevacizumab (2020)(27) | II | 42 | 12 (35) papillary 10 (29) chromophobe 1 (3) medullary 5 (15) collecting duct 5 (15) TFE3translocation 9 (26) unclassified |
ORR | 26 | 8.3 months (5.7–10.9) | NR |
| Cabozantinib + atezolizumab (COSMIC, 2021)(29) |
Ib | 32 | 15 (47) papillary 9 (28) chromophobe 1 (3) collecting duct 1 (3) fumarate-hydrase deficient 1 (3) MiT-family translocation 1 (3) translocation unspecified 1 (3) poorly differentiated 1 (3) spindle-cell 1 (3) clear cell |
ORR | 31 (20–44) | 9.5 (6.4–18.3) 1-year PFS: 39% |
NR |
| Cabozantinib + nivolumab (2022)(30) |
II | 40 | 32 (80) papillary 2 (5) translocation unspecified 6 (15) unclassified |
ORR | 47.5 (31.5–63.9) | 12.5 (6.3–16.4) | 28 (16.3–NE) |
| Nivolumab + ipilimumab (Checkmate 920, 2022)(31) | IIIb/IV | 52 | 18 (35) papillary 7 (13) chromophobe 1 (2) medullary 2 (4) collecting duct 2 (4) translocation, unspecified 22 (42) unclassified |
Grade ≥3 immune-mediated adverse events | 19.6 (9.4–33.9) | 3.7 (2.7–4.6) | 21.2 (16.6–NE) |
| Pembrolizumab + lenvatinib (KEYNOTE-B61, 2023)(33) | II | 158 | 93 (59) papillary 29 (18) chromophobe 6 (4) translocation 9 (6) other 21 (13) unclassified |
ORR | 49 (41–57) | 18 (14–NR) 1-year PFS = 63% |
NR 1-year OS = 82% |
ORR: overall response rate, mPFS: median progression-free survival, OS: overall survival, NA: not assessed, NR: not reached, NE: not evaluated.