Gastrointestinal Stromal Tumor, Malignant
Conditions
Brief summary
Imatinib (IM) has significantly enhanced the prognosis of patients (pts) with advanced gastrointestinal stromal tumors (GISTs). The clinical outcomes may correlate with IM exposure. However, the efficacy threshold, particularly based on different primary KIT mutant, remains undefined. The objective of this study is to establish the efficacy threshold of imatinib (IM) plasma trough concentration (Cmin) at steady-state in Chinese patients with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations.
Detailed description
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The majority of GIST are driven by activating mutuations of KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA, 10-15%), in which KIT exon 11 mutation (52-58%) and KIT exon 9 mutation (6-9%) are the most common types of KIT mutations. Patients with different activating KIT mutations have different sensitivity to imatinib therapy. In the first-line therapy, patients with KIT exon 11 mutation receiving Imatinib with standard dose of 400mg/d has the best therapeutic effect. Patients with KIT exon 9 mutation have poor sensitivity to the standard dose of imatinib, while higher doses can lead to better outcomes. The clinical outcomes may correlate with IM exposure. However, the efficacy threshold of imatinib in Chinese patients with advanced GIST remains unclear. The investigators aim to establish the efficacy threshold of imatinib plasma trough concentration (Cmin) at steady-state in Chinese patients with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations.
Interventions
DRUGImatinib
The long-term maintenance dose of every patient was determined by the physician based on the guidelines and the patients' individual conditions such as adverse reactions.
Sponsors
First Affiliated Hospital, Sun Yat-Sen University
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed metastatic or recurrent GIST * Aged 18 or older * Treated with imatinib as first-line therapy * Had imatinib Cmin measurement at steady state(at least one month after treatment) ≥2 times under long-term maintenance dose of regular medication * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2
Exclusion criteria
* Poor appliance * Important treatment data missing * Combined use of CYP enzyme inducers or inhibitors, such as rifampicin, carbamazepine, ketoconazole, ritonavir, rifamequal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | through study completion, an average of 1 year | Progression free survival (PFS) was defined as time from initiation of imatinib treatment until disease progression, as assessed by Choi criteria, or death caused by any reason. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| objective response rate | through study completion, an average of 1 year | Objective response rate (ORR) was defined as rate of Complete Response (CR) and Partial Response (PR). |
| Overall survival | through study completion, an average of 1 year | Overall survival (OS) was defined as time from initiation of imatinib treatment until death caused by any reason. |
Countries
China
Outcome results
None listed