Table 2.
TTE modeling and logistic regression results
| Parametric TTE models for PFS, iPFS, and OS with time‐varying daily AUC | |
|---|---|
| TTE model, coefficient | Hazard ratio (95% CI) |
| PFS | |
| Log2(AUC/AUCREF) | 0.81 (0.75–0.88) |
| Log sum baseline target lesions | 1.80 (1.39–2.35) |
| iPFS | |
| Log2(AUC/AUCREF) | 0.78 (0.74–0.83) |
| OS | |
| Log2(AUC/AUCREF) | 0.78 (0.73–0.84) |
| Log sum baseline target lesions | 1.92 (1.40–2.63) |
| Logistic regression estimates for ORR and time‐averaged AUC | |||
|---|---|---|---|
| Exposure metric, covariate | β | SD | P value |
| Time‐averaged AUC until best response | |||
| Intercept | 2.0544 | 1.8669 | 0.271 |
| Log (time‐averaged AUC until best response) | −0.1717 | 0.1968 | 0.383 |
| Time‐averaged AUC until end of treatment | |||
| Intercept | 2.2875 | 1.8889 | 0.226 |
| Log (time‐averaged AUC during treatment) | −0.1956 | 0.1983 | 0.324 |
| Logistic regression estimates for iORR and time‐averaged AUC | |||
|---|---|---|---|
| β | SD | P value | |
| Time‐averaged AUC until best intracranial response | |||
| Intercept | −4.7783 | 3.4094 | 0.161 |
| Log (time‐averaged AUC until best intracranial response) | 0.5605 | 0.3615 | 0.121 |
| Time‐averaged AUC until end of treatment | |||
| Intercept | −4.868 | 3.489 | 0.163 |
| Log (time‐averaged AUC during treatment) | 0.567 | 0.368 | 0.123 |
AUC, area under the concentration‐time curve; AUCREF, AUC under the reference regimen of 90 mg once daily; CI, confidence interval; iORR, intracranial objective response rate; iPFS, intracranial progression‐free survival; ORR, objective response rate; OS, overall survival; PFS, progression‐free survival; SD, standard deviation; TTE, time to event.