Table 3.
Summary of the findings for the trials in which proportionality of the hazards was not satisfied*
| Trial | Outcome | Median follow-up time, y | Treatment group | HR (95% CI)† | P‡ | Change point, y, τ | First interval, ≤ τ | Second interval, > τ | ||
|---|---|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | |||||||
| B-05 | DFS | 21.0 | Placebo | Ref | ||||||
| P | 0.83 | .004 | 1.14 | 0.45 | .001 | 1.02 | .88 | |||
| (0.66 to 1.05) | (0.27 to 0.73) | (0.78 to 1.35) | ||||||||
| Recurrence | P | 0.78 | .002 | 1.14 | 0.39 | <.001 | 1.03 | .84 | ||
| (0.60 to 1.02) | (0.23 to 0.66) | (0.75 to 1.43) | ||||||||
| B-11 | DFS | 12.7 | PF | Ref | ||||||
| PAF | 0.81 | .002 | 4.47 | 0.68 | <.001 | 1.44 | .08 | |||
| (0.67 to 0.97) | (0.55 to 0.85) | (0.96 to 2.18) | ||||||||
| Recurrence | PAF | 0.75 | .01 | 3.79 | 0.65 | <.001 | 1.23 | .37 | ||
| (0.61 to 0.92) | (0.52 to 0.83) | (0.78 to 1.92) | ||||||||
| LR Recurrence | PAF | 0.59 | .006 | 3.81 | 0.48 | <.001 | 1.62 | .24 | ||
| (0.43 to 0.81) | (0.33 to 0.68) | (0.73 to 3.61) | ||||||||
| B-12 | OS | 20.3 | PF+TAM | Ref | ||||||
| PAF+TAM | 1.02 | .002 | 2.79 | 0.54 | .005 | 1.13 | .15 | |||
| (0.88 to 1.19) | (0.35 to 0.83) | (0.96 to 1.33) | ||||||||
| B-14 | DFS | 20.4 | Placebo | Ref | ||||||
| TAM | 0.74 | <.001 | 3.42 | 0.53 | <.001 | 0.84 | .002 | |||
| (0.67 to 0.82) | (0.44 to 0.65) | (0.75 to 0.94) | ||||||||
| Recurrence | TAM | 0.59 | .006 | 3.47 | 0.46 | <.001 | 0.70 | <.001 | ||
| (0.51 to 0.68) | (0.37 to 0.58) | (0.58 to 0.84) | ||||||||
| LR recurrence | TAM | 0.47 | .001 | 9.08 | 0.35 | <.001 | 0.79 | .23 | ||
| (0.37 to 0.60) | (0.26 to 0.48) | (0.54 to 1.16) | ||||||||
| B-16 | OS | 16.1 | TAM | Ref | ||||||
| AC+TAM | 0.89 | .002 | 3.47 | 0.51 | .001 | 1.03 | .74 | |||
| (0.74 to 1.07) | (0.34 to 0.76) | (0.84 to 1.27) | ||||||||
| DFS | AC+TAM | 0.84 | .003 | 3.85 | 0.63 | <.001 | 1.05 | .69 | ||
| (0.71 to 0.99) | (0.49 to 0.81) | (0.84 to 1.31) | ||||||||
| B-20 | LR recurrence | 14.6 | TAM | Ref | ||||||
| M→F+TAM | 0.76 | .02 | 3.8 | 0.59 | .07 | 0.91 | .68 | |||
| (0.53 to 1.08) | (0.34 to 1.03) | (0.57 to 1.45) | ||||||||
| CMF+TAM | 0.35 | 0.09 | <.001 | 0.58 | .04 | |||||
| (0.22 to 0.55) | (0.03 to 0.29) | (0.34 to 0.99) | ||||||||
| B-23 | DFS | 11.0 | CMF±TAM | Ref | ||||||
| AC±TAM | 1.13 | .001 | 1.5 | 0.66 | .03 | 1.31 | .005 | |||
| (0.96 to 1.34) | (0.46 to 0.96) | (1.08 to 1.59) | ||||||||
| Recurrence | AC±TAM | 1.06 | .006 | 1.5 | 0.65 | .04 | 1.30 | .05 | ||
| (0.85 to 1.32) | (0.43 to 0.98) | (1.00 to 1.70) | ||||||||
| LR recurrence | AC±TAM | 1.14 | <.001 | 1.93 | 0.50 | .02 | 2.03 | .004 | ||
| (0.81 to 1.62) | (0.28 to 0.89) | (1.26 to 3.28) | ||||||||
| B-31 | Distant recurrence | 9.0 | AC→T1 | Ref | ||||||
| AC→T1+H | 0.51 | .02 | 1.32 | 0.81 | .35 | 0.45 | <.001 | |||
| (0.42 to 0.64) | (0.53 to 1.25) | (0.35 to 0.57) | ||||||||
* All statistical tests were two-sided. A = adriamycin; C = cyclophosphamide; CI = confidence interval; DFS = disease-free survival; F = 5-fluorouracil; H = herceptin; HR = hazard ratio; LR = local-regional; M = methotrexate; OS = overall survival; P = L-Phenylalanine mustard; TAM = tamoxifen; T1 = taxol; y = years.
† Assuming proportionality of hazards.
‡ For statistical significance of time-dependent treatment effect (P value for in [1] with Z(t), as defined in [2]).