TABLE 1.
Summary of Phase III Perioperative Cisplatin-Based Chemotherapy Clinic Trials in Patients with Muscle-Invasive Bladder Cancer
| Stadler (p53) | Cognetti | Paz-Ares | Sternberg | Grossman | MRC/EORTC | |
|---|---|---|---|---|---|---|
| Chemotherapy | Adjuvant MVAC × 3 | Adjuvant GC × 4 | Adjuvant PGC × 4 | Adjuvant ddMVAC/ GC/MVAC × 4 | Neoadjuvant MVAC | Neoadjuvant CMV |
| Patients | T1 and T2 negative LN | T2G3, T3 to T4, N0–2 | T3 to T4, N0 to N2 | T3 to T4 and/or pT × N1 to N3 | T2 to T4aN0 | T2 to T4aN0 |
| Design | ||||||
| α error | 5% | 5% | 5% | 5% | 5% | 5% |
| Power | 90% | 80% | 80% | 80% | 80% | 90% |
| Endpoint | Recurrence | OS | OS | OS | OS | OS |
| 0.5 to 0.3 at 3 years (20%) | 50% to > 60% at 2 years (10%) | 50% to > 65% at 2 years (15%) | 35% to > 42% at 5 years (7%) | 35% to > 42% median OS (50%) | 50% to > 60% at 2 years (10%) | |
| Hazard Ratio | 0.52 | 0.75 | 0.77 | 0.826 | ||
| Planned Sample Size | 190 | 610 | 340 | 660 (originally 1,344) | 298 | 915 |
| Results | ||||||
| Patients randomized | 114 (499 tested and 272 +p53) | 192 | 142 | 284 | 307 | 976 |
| Years to Accrue | 9 | 6 | 7 | 6 | 11 | 6 |
| 5-Year Recurrence (Observation vs Chemotherapy) | TTR, 0.20; p = 0.62; HR, 0.78 | DFS, 42.3% vs. 37.2%; p = 0.70; HR, 1.08; all, 40% | 3 years 44% vs. 73%; p < 0.0001; HR, 0.36; all, 54% | PFS, 31.8% vs. 47.6%; p = < 0.0001; HR, 0.54 | 5-year DFS, 32% vs. 39%; 10-year DFS, 20% vs. 27% p = 0.008; HR, 0.82 | |
| 5-Year OS (Observation vs. Chemotherapy) | 85% (both arms) | 53.7% vs. 43.4%; p = 0.24; HR, 1.29; all, 48.5% | 31% vs. 60%; p < 0.0009; HR, 0.44; all, 49% | 47.7% vs. 53.6%; p = 0.13; HR, 0.78; all, 38.6% | 43% vs. 57%; p = 0.06 | 5-year OS, 43% vs. 49%; 10-year OS, 30% vs. 36%; p = 0.037; HR, 0.84 |
| Median Follow-up | 5.4 years | 35 months | 30 months | 7 years | 8.7 years | 8 years |
Abbreviations: CMV, cispiatin/methotrexate/vinbiastine; dd, dose-dense; DFS, disease-free survival; EORTC, European Organisation for Research and Treatment of Cancer; GC, gemcitabine/cisplatin; HR, hazard ratio; MVAC, methotrexate/vinblastine/doxorubicin/cisplatin; OS, overall survival; PFS, progression-free survival; PGC, paclitaxel/gemcitabine/cisplatin; TTR, time to progression.