Registration trials leading to the FDA approval of PD-1/PD-L1 inhibitors in urothelial carcinoma and renal cell carcinoma
| Study/Agent | Tumor (n) | Line of therapy | Experimental arm | Control arm | Primary endpoint | Ref. |
|---|---|---|---|---|---|---|
| KEYNOTE-052 (phase II)/pembrolizumab | Urothelial carcinoma (n = 370) | First-line cisplatin-ineligible | Pembrolizumab 200 mg every 3 weeks | ORR 24% (95% CI 20-29) | 32 | |
| KEYNOTE-045 (phase III)/pembrolizumab | Urothelial carcinoma (n = 542) | Refractory to platinum-based chemotherapy | Pembrolizumab 200 mg every 3 weeks | Paclitaxel 175 mg/m2 OR docetaxel 75 mg/m2 OR vinflunine 320 mg/m2 | OS 10.3 mos vs. 7.4 mos (HR 0.73, 95% CI 0.59-0.91, p = 0.002)PFS HR 0.98, 95% CI 0.81-1.19, p = 0.42 | 33 |
| CheckMate 275 (phase II)/nivolumab | Advanced urothelial carcinoma (n = 270) | Previously treated with platinum-based chemotherapy | Nivolumab 3 mg/kg every 2 weeks | ORR 28.4% (95% CI 18.9-39.5) for 81 patients with PD-L1 ≥ 5%, 23.8% (95% CI 16.5-32.3) for 122 PD-L1 ≥ 1%, and 16.1% (95% CI 10.5-23.1) for 143 with PD-L1 < 1% | 34 | |
| IMVigor 210 (phase II)/atezolizumab | Urothelial carcinoma (n = 315) | Previously treated with platinum-based chemotherapy | Atezolizumab 1200 mg every 3 weeks | ORR 27% (95% CI 19-37, p < 0.0001) for PD-L1 ≥ 5%, 18% (95% CI 13-24, p = 0.0004) for PD-L1 ≥ 1%, 15% (95% CI 11-20, p = 0.0058) for all patients compared to historical control | 35 | |
| IMVigor 210 (phase II)/atezolizumab | Urothelial carcinoma (n = 119) | First-line cisplatin-ineligible | Atezolizumab 1200 mg every 3 weeks | ORR 23% (95% CI 16-31) in total population | 36 | |
| Study 1108 (phase II)/durvalumab | Urothelial carcinoma (n = 191) | Second-line | Durvalumab 10 mg/kg every 2 weeks | ORR 17.8% (95% CI 12.7-24.0) in all patients, 27.6% (95% CI 19.0-37.5) for PD-L1 ≥ 25%, and 5.1% (95% CI 1.4-12.5) for PD-L1-negative | 38 | |
| JAVELIN Solid Tumor (phase I)/avelumab | Urothelial carcinoma (n = 249) | Second-line | Avelumab 10 mg/kg every 2 weeks | ORR 17.4% (95% CI 11.9-24.1, complete response in 6.2%) for 61 post-platinum patients ≥6 months of follow-up | 40 | |
| CheckMate 025 (phase III)/nivolumab | Advanced RCC (n = 821) | Second-line | Nivolumab 3 mg/kg every 2 weeks | Everolimus 10 mg daily | OS 25.0 mos vs. 19.6 mos (HR 0.73, 98.5% CI 0.57-0.93, p = 0.002) | 41 |
FDA Food and Drug Administration, PD-1 programmed cell death 1, PD-L1 programmed death ligand 1, ORR overall response rate, CI confidence interval, OS overall survival, HR hazard ratio, PFS progression-free survival, RCC renal cell carcinoma