Molecular preselection of pediatric patients with solid tumors treated with tyrosine kinase inhibitors

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).
A systematic literature review was performed to identify studies reporting ORR (till July 2023). The review was non-registered and non-meta-analytic.
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.
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.