Table 2.
Sample Size Estimates for FOCUS4 Trial
| Maximum No. of Events Required |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Molecular Cohort | Random Allocation Ratio | Phase | Outcome | Stage | Target HR | Total | Control Arm | Estimated Cumulative Analysis Time (months) | Maximum No. of Patients Required |
| BRAF mutation (trial A) | 2:1 | II | PFS | 1 | 0.5 | 41 | 16 | 20.4 | 61 |
| PFS | 2 | 0.5 | 76 | 28 | 32.5 | 97 | |||
| III | PFS | 3 | 0.5 | 118 | 42 | 46.5 | 139 | ||
| OS | 4 (potential) | 0.65 | 217 | 79 | 100.4 | 301 | |||
| PIK3CA mutation and/or PTEN loss (trial B) | 2:1 | II | PFS | 1 | 0.65 | 107 | 40 | 17.0 | 170 |
| PFS | 2 | 0.65 | 197 | 71 | 26.5 | 264 | |||
| III | PFS | 3 | 0.65 | 303 | 107 | 37.2 | 373 | ||
| OS | 4 (potential) | 0.7 | 289 | 109 | 54.6 | 546 | |||
| KRAS or NRAS mutation (trial C) | 2:1 | II | PFS | 1 | 0.65 | 109 | 41 | 16.1 | 177 |
| PFS | 2 | 0.65 | 198 | 72 | 22.8 | 273 | |||
| III | PFS | 3 | 0.65 | 302 | 107 | 31.4 | 378 | ||
| OS | 4 (potential) | 0.7 | 287 | 109 | 50.6 | 574 | |||
| All wild type (trial D) | 2:1 | II | PFS | 1 | 0.65 | 109 | 41 | 20.0 | 180 |
| PFS | 2 | 0.65 | 198 | 72 | 30.6 | 275 | |||
| III | PFS | 3 | 0.65 | 301 | 107 | 42.3 | 381 | ||
| OS | 4 (potential) | 0.7 | 289 | 109 | 60.8 | 547 | |||
Abbreviations: HR, hazard ratio; OS, overall survival; PFS, progression-free survival.