Table 4.
PD-L1 expression and efficacy outcome
| Endpoint | Analysis set | Cut-off PD-L1 | Trial, experimental drugs (IMDC subgroups) PD-L1 positive patients (%) experimental versus sunitinib |
||
|
CA209214 Nivolumab/ipilimumab (intermediate/high) |
KEYNOTE-426 Pembrolizumab (all risk group) |
JAVELIN renal 101 Avelumab (all risk group) |
|||
| 284 (66.8)/278 (65.9) | 243 (56.3)/254 (59.2) | 270 (61.6)/290 (59.3) | |||
| OS HR (95% CI) |
ITT | 0.63 (0.44 to 0.89) |
0.59 (0.45 to 0.78) |
0.80 (0.616 to 1.027) |
|
| PD-L1 | <1% | 0.73 (0.56 to 0.96) |
0.54 (0.32 to 0.90) |
0.79 (0.484 to 1.277) |
|
| >1% | 0.45 (0.29 to 0.71) |
0.63 (0.44 to 0.91) |
0.83 (0.596 to 1.151) |
||
| PFS HR (95% CI) |
ITT | 0.82 (0.64 to 1.05) |
0.69 (0.56 to 0.84) |
0.69 (0.57 to 0.83) |
|
| PD-L1 | <1% | 1.06 (0.87 to 1.36) |
0.85 (0.61 to 1.17) |
0.87 (0.622 to 1.220) |
|
| >1% | 0.47 (0.34 to 0.64) |
0.61 (0.48 to 0.79) |
0.62 (0.49 to 0.777) |
||
| ORR % (95% CI) Experimental arm versus comparator |
ITT | 41.6 vs 26.5 (36.9 to 46.5)–(22.4 to31.0) |
59.3 vs 35.7 (54.5 to 63.9)–(31.1 to 40.4) |
52.5 vs 27.3 (47.7 to 57.2)–(23.2 to 31.6) |
|
| PD-L1 | <1% | 37.3 vs 28.4 (31.7 to 43.2)–(23.2 to 34.1) |
56.3 vs NR (48.4 to 63.9) |
49,2 vs 29.2 (40.4 to 58.1)–(21.2 to 38.2) |
|
| >1% | 58 vs 21.9 (47.7 to 67.8)–(14.7 to 30.6) |
60.5 vs NR (54.0 to 66.7) |
55.9 vs 27.2 (49.8 to 61.9)–(22.2 to 32.8) |
||
Test used for tumour PD-L1 expression (≥1% vs <1%): study CA209214: Dako PD-L1 IHC 28–8 pharmDx test; study KEYNOTE-426: PD-L1 IHC 22C3 pharmDx assay; study JAVELIN Renal 101: Ventana PD-L1 (SP263) assay (Ventana Medical Systems).
IMDC, International Metastatic RCC Database Consortium; ITT, intent to treat; NR, not reported; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival.