Table 2.
Exposure to palbociclib or placebo (safety population)
| Pooled analysis |
PALOMA-1 |
PALOMA-2 |
PALOMA-3 |
|||||
|---|---|---|---|---|---|---|---|---|
| Exposure | Palbociclib + endocrine therapy (n = 872) | Endocrine therapy ± placebo (n = 471) | Palbociclib + endocrine therapy (n = 83) | Endocrine therapy (n = 77) | Palbociclib + endocrine therapy (n = 444) | Endocrine therapy + placebo (n = 222) | Palbociclib + endocrine therapy (n = 345) | Endocrine therapy + placebo (n = 172) |
| Treatment duration, mo | ||||||||
| Median | — | — | 13.83 | 7.59 | 19.81 | 13.57 | 10.84 | 4.50 |
| Range | — | — | 0.23−53.06 | 0.92−40.77 | 0.03−34.07 | 0.33−35.18 | 0.03−19.58 | 0.46−20.07 |
| Total person-years exposure | 1017.8 | 423.8 | 127.0 | 76.4 | 627.3 | 258.2 | 263.5 | 89.3 |
| Average daily dose, mg | ||||||||
| Median | — | — | 125 | — | 125 | 125 | 125 | 125 |
| Range | — | — | 79−267* | — | 77−125 | 105−126 | 78−131 | 104−129 |
| Relative dose intensity†, % | ||||||||
| Median | — | — | 100 | — | 93.0 | 99.6 | 89.8 | 100 |
| Range | — | — | 95−100 | — | 40−110 | 56−105 | 22−107 | 80-100 |
| Mean | — | — | 99.5 | — | 86.8 | 98.2 | 85.6 | 97.1 |
| Standard deviation | — | — | 1.04 | — | 14.5 | 5.52 | 15.4 | 6.0 |
| Dose modifications (any cause) | ||||||||
| Dose reductions‡, No. (%) | ||||||||
| ≥1 dose reductions | 322 (36.9) | 6 (1.5)§ | 34 (41.0) | — | 160 (36.0) | 3 (1.4) | 128 (37.1) | 3 (1.7) |
| 1 dose reduction | 214 (24.5) | 6 (1.5)§ | 20 (24.1) | — | 97 (21.8) | 3 (1.4) | 97 (28.1) | 3 (1.7) |
| 2 dose-level reductions | 116 (13.3) | 0§ | 12 (14.5) | — | 63 (14.2) | 0 | 41 (11.9) | 0 |
| Dose interruptions‖, No. (%) | 646 (74.1) | 220 (46.7) | 50 (60.2) | 22 (28.6) | 310 (69.8) | 94 (42.3) | 286 (82.9) | 104 (60.5) |
| Cycle delays¶, No. (%) | 560 (64.2) | 82 (20.8)§ | 70 (84.3) | — | 303 (68.2) | 60 (27.0) | 187 (54.2) | 22 (12.8) |
*
Maximum value pertains to a single patient who was misdosed. — = no data.
†
Relative dose intensity = [(actual dose)/(intended dose)]*100%.
‡
Dose reduction is any dose reduction from the initial prescribed dose regardless of its duration; dose interruptions are not counted as reduction.
§
Denominator is n = 394, includes patients in the endocrine therapy plus placebo arms of PALOMA-2 and -3 only.
‖
Includes any missing dose, gaps within a cycle, or not completing 21 doses per cycle (except last cycle).
¶
Defined as any cycle start delay (PALOMA-1), delays beyond 31 days (PALOMA-2), or delays of two or more days (cycles 1 and 2) or seven or more days (cycle 3 or later; PALOMA-3).