Table 1.
Neoadjuvant clinical trials.
| Agent | Administration Conditions | Trial Name/NCT Number | Clinical Stage | Patients | Age (Median; IQR); Male% | PD-L1 + | Phase | Toxicity Grade 3–4 * (%) |
Results |
|---|---|---|---|---|---|---|---|---|---|
| Single-agent ICI | |||||||||
| Pembrolizumab [61] | 200 mg; 3 cycles, 3 weekly | PURE-01/NCT02736266 | T2-3aN0M0 | 114 | 66 (60–71); 82% | 59% | II | 2.6% | Overall pCRR: 37% (39.8% of the PD-L1 +) |
| Atezolizumab [62] | 75 pts: full treatment (2 cycles, 3 weekly); 20 pts: only 1 cycle |
ABACUS/NCT02662309 | T2-4aN0M0 | 95 | 74 (68–77); 85% | 41% | II | 14.7% | Overall pCRR: 31% (37% of the PD-L1 +) |
| Combination therapy | |||||||||
| Pembrolizumab plus Gem ± Cis [63] | Pembro: 200 mg (day 8) for 5 doses; Cis: 70 mg/m2 (day 1); Gem: 1000 mg/m2 (days 1 + 8), every 3 weeks for 4 cycles | GU14-188/NCT02365766 | T2-4N0M0 (T2: 50%) |
40 | 65 (−); 75% | 52% | Ib/II | 32.5% Grade 3–4 cytopenia: 57% |
T1N0M0 at RC: 60%; 1-year OS: 94% |
| Nivolumab plus Gem ± Cis [64] | Cis: 70 mg/m2 (day 1), Gem: 1000 mg/m2 (day 1 + 8), Nivo: 360 mg (day 8) every 3 weeks for 4 cycles | BLASST-1/NCT03294304 | T2-4aN0-1M0 (T2N0: 90%) | 43 | - | - | II | 20% | Overall pCRR: 65.8%; downstaging: 83% |
| Nivolumab plus Ipilimumab [65] | Ipi: 3 mg/kg (day 1), Ipi + Nivo: 1 mg/kg (day 22), Nivo: 3 mg/kg (day 43) | NABUCCO/NCT03387761 | T3-4aN0M0 or N+ |
24 | - | 60% | Ib | 42% | Overall pCRR: 46% |
PCRR: pathologic complete response rate; Gem: gemcitabine; Cis: cisplatin; RC: radical cystectomy; OS: overall survival; IQR: interquartile rate. * Adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Event classification, version 5.0.