Abstract 82P
Background
The results of studies with tyrosine kinase inhibitors (TKIs) in the treatment of paediatric solid tumors have been unsatisfactory. As TKIs are known to affect only selected molecular pathways, the aim of this analysis was to determine whether a molecular preselection of patients increases a response to treatment with TKIs.
Methods
A literature search including PubMed, the Cochrane Library, EU and US clinical trial databases and the European Medicines Agency website registry was conducted to identify available results of clinical interventional studies in paediatric patients with solid tumors other than CNS tumors who were treated with TKIs. Studies had to report results for overal response rate (ORR). Studies using combination treatment and insufficient dose as well as studies which enrolled benign plexiform neurofibromas were excluded from the analysis. Response rate was compared for arms that used a personalized strategy (biomarker selection) vs those that did not.
Results
The final dataset included 15 studies (358 patients) which molecularly preselected patients and 17 studies (336 patients) which did not. Studies included almost exclusively patients with relapsed, refractory, or advanced tumors. A significant difference in response to treatment was identified between studies which recruited only molecularly preselected patients and so called all-comers studies (median ORR 30% vs 2%; p = 0.02). Insufficient molecular characterization of tumors was identified in the studies which molecularly preselected patients: only 4 studies investigated molecular aberrations beyond those falling under the mechanism of action of the tested TKI.
Conclusions
Molecular background of paediatric solid tumours must be taken into account when using TKIs as this improves a response of patients to treatment. The current molecular preselection criteria are insufficient and need to be improved. Further molecular aberrations beyond those falling under the mechanism of action of the tested product need to be taken into account to improve targeting of complex tumour microenvironment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.