AbstractBackgroundSignificant challenges persist in treating children with rare, relapsed, or refractory malignancies. Novel molecularly targeted drugs promise improved outcomes for these children with reduced toxicity. However, there is often limited evidence to substantiate their clinical efficacy and guide their use. This raises issues for clinical decision‐making, ethical concerns surrounding equity of access to these often‐expensive agents, and the management of families' expectations for cure. This audit evaluated the off‐label use of novel drugs and associated clinical outcomes in order to guide the development of future clinical and ethical guidelines.AimTo evaluate the patterns in the off‐label use of novel drugs for treating childhood cancer and the associated clinical outcomes to guide prospective studies and inform ethical and clinical governance protocols for the use of these agents.MethodsA retrospective audit was performed for all patients who received novel drugs off‐label as treatment for their malignancy at an Australian pediatric oncology center between 2010 and 2019.ResultsOne hundred patients with 32 unique diagnoses received 133 novel drugs across 124 regimens. Eighty‐four patients received these drugs at the second line of treatment or greater. Novel drug median cost was $15 521 AUD (Range: $6.53 AUD to $258 339 AUD) and was primarily funded by the hospital (N = 60/133, 45.1%) or compassionate access from pharmaceutical companies (N = 52/133, 39.1%). Decision‐making related to novel drugs was inconsistently documented. Ninety‐one of 124 treatment regimens commenced between 2010 and 2019 resulted in objective responses (73.4%), but only 35 were still ongoing upon review in June 2020 (38.5%). Median response duration was 12.6 months (Range: 0‐93.2 months).ConclusionsWhile novel drugs were largely unable to definitively cure patients, most achieved objective responses. Prospective trials and more rigorous documentation are needed to fully inform the future use of these agents given the heterogeneity of their applications.