Off-label prescribing of targeted anticancer therapy at a large pediatric cancer center

Background Off-label drug prescribing is common in pediatric clinical medicine, though the extent and impact of this practice in pediatric oncology has not yet been characterized. Methods We completed a retrospective single-institution cohort study evaluating prevalence, characteristics, and clinical outcomes of off-label prescribing of 108 FDA-approved targeted anticancer drugs in patients < 30 years old treated for cancer from 2007 to 2017. Dosing strategies were adjusted for body size and compared to FDA-approved adult dosing regimen. A composite toxicity endpoint was defined as a patient having unplanned clinic visits, emergency department visits, or unplanned hospital admissions that were at least possibly related to the off-label treatment. Results The overall prevalence of off-label use of targeted therapies was 9.2% (n = 374 patients). The prevalence increased significantly over the study period (P < .0001). Patients treated off-label were more likely to have neuro-oncology diagnoses compared to patients not treated off-label (46% vs 29%;P < .0001). Of the 108 potential agents, 38 (35%) were used by at least one patient. The median starting dose was below the FDA-approved normalized dose for 44.4% of agents. Fifteen percent of patients had a complete response while receiving off-label therapy, 38% experienced toxicity as defined, and 13% discontinued off-label therapy due to toxicity. Conclusions In this real-world evaluation of prescribing at a large pediatric cancer center, off-label prescribing of FDA-approved targeted therapies was common, increasing in prevalence, encompassed a broad sample of targeted agents, and was tolerable. Clinicians commonly start dosing below the equivalent FDA-approved dose.