Correlation Between Imatinib Trough Concentration and Efficacy in Advanced GIST Patients with Different Genotypes

Sun Yat-sen University

Status: Completed

Conditions: Gastrointestinal Stromal Tumor, Malignant

Treatments: Drug: Imatinib

Study type: Observational

Funder types: Other

Identifiers

NCT06628739

No.[2023]184

Details and patient eligibility

About

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.

Full 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.

Enrollment: 168 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

168 participants in 2 patient groups

IM Cmin below deciles boundary

Description:

Patients with imatinib Cmin less than the decile boundary based on each imatinib Cmin distribution decile.

IM Cmin above deciles boundary

Description:

Patients with imatinib Cmin greater than or equal to the decile boundary based on each imatinib Cmin distribution decile.