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Updated: Jan 30, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Molecular preselection of pediatric patients with solid tumors treated with tyrosine kinase inhibitors
Peter Sisovsky1,2, Nikola Gejgusova1, Tomas Fazekas3
1Efficacy Assessment Department, State Institute for Drug Control, Bratislava, Slovakia.
Aim:
To review how molecular preselection and combination treatment affects overall response rate (ORR) in pediatric non-central nervous system (CNS) solid tumors treated with tyrosine kinase inhibitors (TKIs).
Methods:
A systematic literature review was performed to identify studies reporting ORR (till July 2023). The review was non-registered and non-meta-analytic.
Results:
53 clinical studies involving 306 molecularly preselected patients (16 studies), 513 molecularly not preselected patients on TKI monotherapy (26 studies) and 350 molecularly not preselected patients on combination therapy (15 studies) met prespecified criteria for ORR analysis. According to the MINORS score, methodological quality was moderate to poor. Molecular preselection increased median ORR to TKI monotherapy from 0% [95% CI, 0%, 6%] to 36% [95% CI, 27%, 50%], (p = 0.001). Combination treatment increased median ORR from 0% [95% CI, 0%, 6%] to 14% [95% CI, 5%, 26%] in molecularly unselected population (p = 0.003). Comprehensive molecular characterization was absent, less than 20% of studies investigated molecular aberrations beyond the mechanism of action of tested TKI. Only few studies were terminated due to safety issues.
Conclusions:
Molecular background of tumors should be taken into account when using TKIs. The current molecular pre-selection criteria are insufficient and need to be improved.
Insights
Molecular preselection significantly improves tyrosine kinase inhibitor (TKI) response rates in pediatric solid tumors. Current patient selection methods for TKI therapy need enhancement for better outcomes.
Area of Science:
- Oncology
- Pharmacogenomics
- Pediatric Medicine
Background:
- Tyrosine kinase inhibitors (TKIs) are crucial in treating pediatric solid tumors.
- Optimizing TKI efficacy requires understanding molecular drivers and patient selection.
- Current treatment strategies may not fully leverage molecular insights.
Purpose of the Study:
- To review the impact of molecular preselection and combination therapy on overall response rate (ORR) in pediatric non-central nervous system (CNS) solid tumors treated with TKIs.
- To assess the effectiveness of molecularly guided TKI therapy versus standard approaches.
- To identify areas for improvement in molecular preselection criteria for TKI treatment.
Main Methods:
- Systematic literature review of clinical studies reporting ORR for TKI therapy in pediatric solid tumors (up to July 2023).
- Analysis of studies involving molecularly preselected patients, TKI monotherapy, and combination therapy.
- Evaluation of methodological quality using the MINORS score.
Main Results:
- Molecular preselection significantly increased median ORR to TKI monotherapy from 0% to 36% (p=0.001).
- Combination treatment improved median ORR to 14% in molecularly unselected patients (p=0.003).
- Methodological quality was moderate to poor; comprehensive molecular characterization was lacking in most studies.
Conclusions:
- Tumor molecular background is critical for effective TKI use in pediatric solid tumors.
- Current molecular preselection criteria for TKIs are insufficient and require refinement.
- Further research is needed to develop improved molecular profiling and selection strategies for TKI therapy.
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