Multi-tyrosine kinase inhibitors in paediatric soft tissue sarcoma – A review

<h2>Abstract</h2> Neoadjuvant systemic treatment for paediatric patients with soft tissue sarcomas (STS) consists of conventional chemotherapy, predominantly ifosfamide and doxorubicin, with a limited role for innovative therapies. Many multi-tyrosine kinase inhibitors (mTKIs) have been developed in the past decades for the treatment of various types of malignancies. Over a decade ago, the mTKI pazopanib was authorized by the EMA and FDA for the treatment of adults with STS. Paediatric development of innovative treatments often follows years after the first marketing authorisations in adults has been obtained. To date, a series of clinical trials have been conducted investigating the value of mTKIs in paediatric patients with STS. Nevertheless, the positioning of mTKIs in the treatment of paediatric STS remains unclear and selection of mTKIs for clinical trials is more often made on grounds of availability rather than on mechanism of action, efficacy data, or toxicity profile. In this manuscript, we provide an overview of studies evaluating mTKIs in paediatric, adolescent, and adult STS patients, aiming to assist in prioritization of future clinical trials in paediatric STS. We performed a systematic literature review with the purpose of collecting data on activity and safety. The results of 107 relevant clinical trials, including 23 trials conducted in the paediatric population and 84 trials in the adult population, were critically assessed and summarized (Appendix 1). Accelerating the development of innovative treatments in patients with such ultra-rare diseases will require innovative clinical trial designs, and international collaboration is necessary. Considering the age distribution of STS, collaboration between paediatric oncologists and medical oncologists should be considered.