Table 1.
Summary of efficacy results in CA209214
| Overall survival | Intermediate/poor-risk subjects | All randomised (any risk) subjects | ||
| Nivolumab+ipilimumab N=425 |
Sunitinib N=422 |
Nivolumab+ipilimumab N=550 |
Sunitinib N=546 |
|
| Co-primary objective | Secondary objective | |||
| N events (%) | 140 (32.9) | 188 (44.5) | 161 (29.3) | 204 (37.4) |
| Median OS (months)* | N.A. | 25.95 | N.A. | 32.92 |
| Exact 95% CI | (28.16 to N.A.) | (22.08 to N.A.) | – | (N.A. to N.A.) |
| HR (99.8% CI)† | 0.63 (0.44 to 0.89) | 0.68 (0.49 to 0.95) | ||
| p-value‡ | <0.0001 | 0.0003 | ||
| Overall survival (OS) by PD-L1 tumour expression (1% tumour cell membrane expression) | ||||
| Subjects with >1% PD-L1 expression, n/N | 28/100 | 57/114 | 30/113 | 60/127 |
| Median (months) | N.A. | 19.61 | N.A. | N.A. |
| 95% CI | (14.78 to N.A) | (15.47 to N.A.) | ||
| Subjects with <1% PD-L1 expression, n/N (%) | 93/284 | 114/278 | 108/386 | 126/376 |
| Median (months) | N.A. | N.A. | N.A. | 32.92 |
| 95% CI | (28.16 to N.A.) | (23.98 to N.A.) | (N.A. to N.A.) | |
| Subjects with non-quantifiable PD-L1 expression, n/N (%) | 19/41 | 17/30 | 23/51 | 18/43 |
| Median (months) | 24.34 | 15.7 | 24.34 | N.A. |
| 95% CI | (10.12 to N.A.) | (9.76 to N.A.) | (16.99 to N.A.) | (15.70 to N.A.) |
| IRRC-assessed progression-free survival | Co-primary objective | Secondary objective | ||
| N events (%) | 228 (53.6) | 228 (54.0) | 296 (53.8) | 271 (49.6) |
| Median PFS (months)* | 11.56 | 8.38 | 12.42 | 12.32 |
| Exact 95% CI | (8.71 to 15.51) | (7.03 to 10.81) | (9.89 to 16.53) | (9.79 to 15.24) |
| HR (99.1% CI)† | 0.82 (0.64, 1.05) | 0.98 (0.79, 1.23) | ||
| p-value‡ | 0.0331 | 0.8498 | ||
| IRRC-assessed objective response rate (CR+PR)§ | Co-primary objective | Secondary objective | ||
| N responders (%) | 177 (41.6) | 112 (26.5) | 213 (38.7) | 176 (32.2) |
| Exact 95% CI | 36.9 to 46.5 | 22.4 to 31.0 | 34.6 to 42.9 | 28.3 to 36.3 |
| Difference in ORR (95% CI)¶** | 16.0 (9.8 to 22.2) | 7.2 (1.8 to 12.7) | ||
| p-value†† | <0.0001 | 0.0191 | ||
| Best overall response | ||||
| Complete response (CR) (%) | 40 (9.4) | 5 (1.2) | 54 (9.8) | 12 (2.2) |
| Partial response (PR) (%) | 137 (32.2) | 107 (25.4) | 159 (28.9) | 164 (30.0) |
| Stable disease (%) | 133 (31.3) | 188 (44.5) | 199 (36.2) | 232 (42.5) |
| Progressive disease (%) | 83 (19.5) | 72 (17.1) | 99 (18.0) | 78 (14.3) |
| Unable to determine (%) | 31 (7.3) | 50 (11.8) | 38 (6.9) | 59 (10.8) |
*Median computed using the Kaplan-Meier method.
†Stratified Cox proportional hazard model. HR is nivolumab + ipilimumab over sunitinib.
‡Log-rank test stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score (0, 1–2, 3–6) and region (USA, Canada/W Europe/N Europe, ROW) as entered into the IVRS.
§CI based on the Clopper and Pearson method.
¶Strata adjusted difference in overall response rate (ORR; nivolumab + ipilimumab ‒ sunitinib) based on the DerSimonian and Laird method.
**Stratified by IMDC prognostic risk score (0, 1–2, 3–6) and region (USA, Canada/Western Europe/Northern Europe, Rest of World) as entered into the IVRS.
††Two-sided p value from DerSimonian and Laird Test.
IRRC, independent radiological review committee; N.A., not achieved; PD-L1, programmed death-ligand 1.