Table 3.
Serum trastuzumab emtansine (T-DM1), serum total trastuzumab (TT), and plasma DM-1 pharmacokinetic (PK) parameters for patients in studies TDM3569g (3.6-mg/kg cohort), TDM4258g, TDM4374g, and TDM4688g
| Analyte | Study (no. of patientsa) | Mean (standard deviation) | ||||
|---|---|---|---|---|---|---|
| C max (μg/mL) | AUCinf (day μg/mL) | t 1/2 (day) | V ss (mL/kg) | Clearance (mL/day/kg) | ||
| Serum T-DM1 | TDM3569g (n = 15) | 76.2 (19.1) | 300 (65.8) | 3.1 (0.7) | 58.4 (12.4) | 12.7 (3.56) |
| TDM4258g (n = 101) | 80.9 (20.7) | 457 (129) | 3.53 (0.71) | 28.4 (12.9) | 8.51 (2.69) | |
| TDM4374g (n = 105) | 79.5 (21.1) | 486 (141) | 3.96 (0.96) | 31.2 (10.9) | 8.04 (2.97) | |
| TDM4688g (n = 51) | 75.6 (21.9) | 431 (126) | 4.02 (0.94) | 41.2 (24.5) | 9.17 (3.03) | |
| Serum TT | TDM3569g (n = 15) | 110 (40.3) | 1,144 (857) | 9.1 (4.9) | 50.7 (19.7) | 4.90 (3.23) |
| TDM4258g (n = 101) | 88.0 (30.2) | 1,040 (1,030) | 9.2 (10.9) | 46.5 (58.4) | 5.64 (6.30) | |
| TDM4374g (n = 105) | 89.9 (31.3) | 1,150 (852) | 9.38 (4.90) | 43.2 (16.3) | 4.55 (2.64) | |
| TDM4688g (n = 51) | 95.9 (32.3) | 1,420 (1,390) | 10.3 (6.8) | 41.9 (16.2) | 4.21 (2.43) | |
| Analyte | Study (no. of patientsa) | C max at cycle 1 (ng/mL) |
|---|---|---|
| Plasma DM1b | TDM3569g (n = 15) | 4.57 (1.33) |
| TDM4258g (n = 101) | 5.35 (2.03) | |
| TDM4374g (n = 105) | 5.36 (2.56) | |
| TDM4688g (n = 51) | 5.42 (1.62) |
AUC inf area under the serum concentration versus time curve from time 0 extrapolated to infinity; C max maximum observed concentration; PK pharmacokinetic; V ss volume of distribution at steady state; t 1/2 terminal half-life
aNumber of patients with at least one PK parameter evaluable
bPlasma DM1 concentrations were below the limit of quantification at the majority of time points and, therefore, no formal PK analysis was possible