| General information |
| Database: | DB00442 |
| Objective: | The aim of this study was to characterize trastuzumab population pharmacokinetics (PKs) in patients with human epidermal growth factor receptor 2positive advanced gastric or gastroesophageal junction cancer and the relationship of trastuzumab PK with patient response. |
| Authors: | Cosson VF, et al |
| Title: | Population pharmacokinetics and exposureresponse analyses of trastuzumab in patients with advanced gastric or gastroesophageal junction cancer. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2014 |
| PMID: | 24519752 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | trastuzumab
|
| Target: | Receptor proteintyrosine kinase erbB2
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced adenocarcinoma of the stomach or gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | trastuzumab plus chemotherapy or chemotherapy alone. |
| Study Type: | an international, phase III, randomized, openlabeltrial |
| Key Patients Feature: | patients with human epidermal growth factor receptor 2positive inoperable, locallyadvanced, recurrent, or metastatic adenocarcinoma of thestomach or geJ. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | trastuzumab plus chemotherapy or chemotherapy alone. |
| Treatment Info: | A nonlinear mixed effects PK model was built using data from the ToGA study. patients were randomized to intravenous trastuzumab plus chemotherapy or chemotherapy alone. The influence of demographic, laboratory, and disease characteristics on PK parameters was assessed. |
| Primary End Point: | An exploratory exposureresponse analysis compared various PK parameters at steady state with best overall tumor response and overall survival (OS). |
| Secondary End Point: | NA |
| Patients Number: | 266 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | In the <17.3 ¦Ìg/mL group, CR 5.6%, PR 40.7%, SD 22.2%, PD 31.5%;In the more than and equal to 17.3 and <27.6 ¦Ìg/mL group, CR 5.5%, PR 49.1%, SD 36.4%, PD 9.1%; In more than and equal to 27.6 and <36.9 ¦Ìg/mL group, CR 5.5%, PR 49.1%, SD 36.4%, PD 9.1%; In the more than and equal to 36.9 ¦Ìg/mL group, CR 8.5%, PR 55.9%, SD 27.1%, PD 8.5%; |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | In the advanced gastric cancer population, trastuzumab PK was best described by a twocompartment model with parallel linear and nonlinear elimination. Predicted PK exposure was lotheyr than previously reported for breast cancer. Patients with the lotheyst Cmin had a shorter OS and the highest PD rate, but a distinct correlation was not observed for tumor response. |