Table 1.
Results of the clinical trials of the medical treatment for the urological cancers.
| Trial | Therapeutic line | Treatment | Cancer type | Patients | Primary endpoint/Result | Secondary endpoint/Result |
|---|---|---|---|---|---|---|
| Renal cell cancer | ||||||
| Checkmate-214 (9) | 1st line | Nivolumab + Ipilimumab vs. Sunitinib |
ccRCC | n=1096 (554/546) IMDC risk score Fav. 125/124 Int. 334/333 Poor. 91/89 |
Coprimary endpoint: OS, ORR, PFS in IMDC int. or poor risk OS: NR vs 26.0 m (HR 0.63, p<0.001) ORR: 42% vs. 27% (p<0.001) PFS: 11.6m vs 8.4m (HR 0.83, p=0.03) |
OS, PFS, ORR in ITT population OS: NR vs. 32.9m (HR 0.68, p<0.001) ORR: 39% vs 32 (p=0.02, not significant) PFS: 12.4m vs. 12.3m (HR 0.98, p=0.85) |
| Javelin Renal 101 (10) | 1st line | Pembrolizumab + Avelumab vs. Sunitinib |
ccRCC | n=886 (442/444) PD-L1+: (n=560) |
PFS, OS with PD-L1 positive tumors OS: immature data PFS: 13.8m vs. 7.2m (HR 0.61, p<0.001) |
PFS in overall population: 13.8m vs. 8.4m (HR 0.69, p<0.001) ORR with PD-L1 positive tumors: 55.2% vs. 25.5% |
| Keynote-426 (11) | 1st line | Pembrolizumab + Axitinib vs. Sunitinib |
ccRCC | n=861 (432/429) | OS, PFS in ITT population OS: NR vs. NR (HR 0.53, p<0.0001) PFS: 15.1m vs 11.1m (HR 0.69, p<0.001) |
ORR: 59.3% vs. 35.7% (p<0.001) |
| METEOR trial (12) | 2nd line | Cabozantinib vs. Everolimus |
ccRCC | n=658 (330/328) | PFS: 7.4m vs. 3.8m (HR 0.58, p<0.001) |
OS: NR vs. NR (HR 0.67, p=0.005) ORR: 21% vs. 5% (p<0.001) |
| CABOSUN trial (13) | 1st line (Phase2) | Cabozantinib vs. Sunitinib |
ccRCC | n=157 (79/78) IMDC risk score: int. or poor |
PFS: 8.2m vs. 5.6m (HR 0.66, p=0.012) |
OS: 30.3m vs. 21.8m (Adjusted HR 0.80) ORR: 46% vs. 18% |
| Checkmate 9ER (14) | 1st line | Cabozantinib + Nivolumab vs. Sunitinib |
ccRCC | n=631 (323/328) | PFS: 16.6m vs 8.3m (HR 0.51, p<0.001) |
OS: NR vs. NR (HR 0.60, p=0.001) ORR: 55.7% vs. 27.1% (p<0.001) |
| CLEAR trial (15) | 1st line | Lenvatinib (L) + Pembrolizumab (P) vs. Lenvatinib + Everolimus (E) vs. Sunitinib (S) |
ccRCC | n=1069 (355/357/357) | PFS (L+P vs. S): 23.9 vs. 9.2m (HR 0.39, p<0.001) PFS (L+E vs. S): 14.7m vs. 9.2m (HR 0.65, p<0.001) |
OS (L+P vs. S): NR vs. NR (HR 0.66, p=0.005) OS (L+E vs. S): NR vs. NR (HR 1.15, p=0.30) |
| Keynote-564 (16) | Adjuvant therapy | Pembrolizumab vs. Placebo |
ccRCC | n=994 (496/498) Intermediate risk (427/433)† High risk (40/36)† M1 NED (29/29)† |
DFS: 12m rate 85.7% vs. 76.2% 24m rate 77.3% vs. 68.1% (HR 0.68, p=0.0010) |
OS: (HR 0.54, p=0.0164 not significant) |
| Urothelial cancer | ||||||
| Javelin Bladder 100 (17) | Maintenance after 1st line (platinum doublet) | Avelumab vs. Best Supportive Care |
Urothelial carcinoma | n=700 (350/350) PD-L1+ tumor 358 (189/169) Upper tract (106/81) Lower tract (244/269) |
OS in overall population: 21.4m vs. 14.3m (HR 0.69, p=0.001) OS in PD-L1+tumor: NE vs. 17.1m (HR 0.56, p<0.001) |
PFS in overall population: 3.7m vs. 2.0m (HR 0.62) PFS in PD-L1+ tumor: 5.7m vs. 2.1m (HR 0.56) |
| EV-301 trial (8) | 3rd line | Enfortumab Vedotin vs. Docetaxel/Paclitaxel/Vinflunine |
Urothelial carcinoma | n = 608 (301/307) | OS: 12.88m vs. 8.97m (HR 0.70, p=0.001) |
PFS: 5.55m vs. 3.71m (HR 0.62, p<0.001) |
| Checkmate274 (18) | Adjuvant therapy | Nivolumab vs. Placebo |
Muscle invasive urothelial carcinoma | n = 709 (353/356) Urinary bladder (279/281) Renal pelvis (44/52) Ureter (30/23) |
DFS in ITT population: DFS at 6m: 74.9% vs. 60.3% DFS at 12m: 62.8% vs 46.6% (HR 0.70, p<0.001) DFS in tumors positive for PD-L1: DFS at 6m: 74.5% vs. 55.7% DFS at 12m: 67.2% vs 45.9% (HR 0.55, p<0.001) |
Survival free from recurrence outside the urothelial tract: 40.5m vs. 29.5m alive and free from distant metastasis at 6m (ITT population): 82.5% vs. 69.8% (HR for distant metastasis or death 0.75) alive and free from distant metastasis at 6m (PD-L1+ population): 78.7% vs. 65.7% (HR for distant metastasis or death 0.61) |
| Prostate cancer | ||||||
| Keynote-12, 28, 16, 158, 164 (19) | KN-12: ≥1 prior regimen KN-28: ≥1 prior regimen KN-16: -CRC: ≥2 prior regimens -non CRC: ≥1 prior regimen KN-158: ≥1 prior regimen KN-164: Prior FP, oxaliplatin, and irinotecan ± anti-VEGF/EGFR |
Pembrolizumab (not randomized) |
Solid tumor | KN-12: n = 6 KN-28: n = 5 KN-16: n = 30 (non CRC) KN-158: n = 19 KN-164: n = 61 |
ORR: 39.6% with a 7% CR Duration of response: from 1.6+ to 22.7+ m with 78% of responses lasting ≥6 m |
– |
| PROfound trial (6) | After ARAT | Olaparib vs. another ARAT |
mCRPC | n = 632 (256/131) Cohort A (n=162/83) had at least one alteration in BRCA1, BRCA2, or ATM |
Imaging-based PFS in cohort A: 7.4m vs. 3.6m (HR 0.34, p<0.001) |
Imaging-based PFS in the overall population: 5.8m vs. 3.5m (HR 0.49, p<0.001) |
IMDC, International Metastatic renal cell cancer Database Consortium; ccRCC, clear cell renal cell cancer; Fav., favorable; Int., Intermediate; OS, Overall survival; PFS, Progression free survival; ORR, Objective response rate; NR, Not reached; NE, could not be estimated; ITT, Intention-to-treat; DFS, Disease free survival; CRC, Colorectal cancer; mCRPC, metastatic castration resistant prostate carcinoma; ARAT, androgen receptor axis targeted agent.
† intermediate risk: pT2, grade4 or sarcomatoid, N0, M0; or pT3, any grade, N0M0, high risk: pT4, any grade, N0, M0; pT any stage, N+, M0, M1 NED: No evidence of disease after primary tumor + soft tissue metastases completely resected ≤ 1year from nephrectomy.