BACKGROUND For patients with advanced gastrointestinal stromal tumors(GISTs)carrying the ckit exon 11 mutation,imatinib(IM)at a standard dosage of 400 mg per day is the preferred first-line treatment.In cases where tr...BACKGROUND For patients with advanced gastrointestinal stromal tumors(GISTs)carrying the ckit exon 11 mutation,imatinib(IM)at a standard dosage of 400 mg per day is the preferred first-line treatment.In cases where treatment with IM fails,there is an urgent need for a more precise assessment method to determine whether to switch therapies or escalate the IM dosage.This approach will enhance clinical decision-making and optimize patient outcomes.AIM To investigate IM plasma concentration’s role in second-line treatment decisions for c-kit 11-mutated advanced GISTs post-IM failure.METHODS Patients with advanced GIST harboring c-kit 11 mutation who experienced failure with IM 400 mg per day as first-line treatment at our hospital were retrospectively analyzed.Patients were categorized into a low plasma(LP)concentration group(LP group,<1100 ng/mL)and high plasma(HP)concentration group(HP group,≥1100 ng/mL).Each group was further subdivided into Group A(dose-escalation group)and Group B(drug-switch group).Baseline characteristics were compared and Kaplan-Meier curves were used to analyze the survival of patients.RESULTS Seventy-five patients were included in the analysis.For the LP group(n=28),Group A(n=14)had longer overall survival(OS)than Group B(n=14)(P=0.02).No differences were observed between the two subgroups in disease control rate(DCR),objective response rate,and progression-free survival(PFS)(P>0.05).For the HP group(n=47),Group B(n=18)had a higher DCR and longer PFS than Group A(n=29)(P=0.008 and P=0.03,respectively).No difference in OS was observed between the two subgroups(P>0.05).CONCLUSION Increasing IM dosage for c-kit 11-mutated advanced GISTs post-IM failure may prolong OS if plasma concentration is<1100 ng/mL.Switching tyrosine kinase inhibitors may improve DCR and PFS if≥1100 ng/mL.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
文摘BACKGROUND For patients with advanced gastrointestinal stromal tumors(GISTs)carrying the ckit exon 11 mutation,imatinib(IM)at a standard dosage of 400 mg per day is the preferred first-line treatment.In cases where treatment with IM fails,there is an urgent need for a more precise assessment method to determine whether to switch therapies or escalate the IM dosage.This approach will enhance clinical decision-making and optimize patient outcomes.AIM To investigate IM plasma concentration’s role in second-line treatment decisions for c-kit 11-mutated advanced GISTs post-IM failure.METHODS Patients with advanced GIST harboring c-kit 11 mutation who experienced failure with IM 400 mg per day as first-line treatment at our hospital were retrospectively analyzed.Patients were categorized into a low plasma(LP)concentration group(LP group,<1100 ng/mL)and high plasma(HP)concentration group(HP group,≥1100 ng/mL).Each group was further subdivided into Group A(dose-escalation group)and Group B(drug-switch group).Baseline characteristics were compared and Kaplan-Meier curves were used to analyze the survival of patients.RESULTS Seventy-five patients were included in the analysis.For the LP group(n=28),Group A(n=14)had longer overall survival(OS)than Group B(n=14)(P=0.02).No differences were observed between the two subgroups in disease control rate(DCR),objective response rate,and progression-free survival(PFS)(P>0.05).For the HP group(n=47),Group B(n=18)had a higher DCR and longer PFS than Group A(n=29)(P=0.008 and P=0.03,respectively).No difference in OS was observed between the two subgroups(P>0.05).CONCLUSION Increasing IM dosage for c-kit 11-mutated advanced GISTs post-IM failure may prolong OS if plasma concentration is<1100 ng/mL.Switching tyrosine kinase inhibitors may improve DCR and PFS if≥1100 ng/mL.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
