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

Abstract

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.

Retrospective evaluation of single patient investigational new drug (IND) requests in pediatric oncology

“…In our experience, single patient INDs were universally approved and were most commonly submitted for patients with relapsed extra‐cranial solid tumors (63%). By comparison, between January 1 st , 2007 and December 31 st , 2017, 34%, 35%, and 29% of patients with new diagnoses at our center were treated for hematologic malignancies, solid tumors or brain tumors, respectively 10 . Interestingly, 21% of single patient IND therapies were administered as part of frontline therapy rather than for patients with relapsed disease.…”

“…By comparison, between January 1 st , 2007 and December 31 st , 2017, 34%, 35%, and 29% of patients with new diagnoses at our center were treated for hematologic malignancies, solid tumors or brain tumors, respectively. 10 Interestingly, 21% of single patient IND therapies were administered as part of frontline therapy rather than for patients with relapsed disease. Many patients had an objective decrease in disease burden as assessed with radiographic scans and bone marrow biopsies, with 24 of 48 patients remaining on treatment for greater than 90 days.…”

Off-Label Medication: From a Simple Concept to Complex Practical Aspects

“…There was an increasing prevalence of off-label use during the study period, with an overall tolerability of use by the studied population, reflected in the small percent of treatment discontinuation. The authors offer, as a possible explanation, that the treatment often starts with a lower, more conservative dose, below the FDA-approved dosing [ 71 ]. Venekamp et al [ 72 ] studied the efficacy and safety of antibiotics in middle ear infection (otitis media) in children.…”

Childhood cancer drugs in China: An overview and comparison of regulatory approvals in China and the United States

“…Childhood cancer drugs in China were mainly traditional chemotherapy drugs, approved for more paediatric cancer indications than those approved in the United States. In the United States, off-label drug use in cancer care is legal and common, [40][41][42][43] and, given state-mandated insurance coverage of cancer drugs for offlabel indications listed in an approved compendium, off-label cancer drug use is reimbursable. [44][45][46][47] Thus, the implications of traditional chemotherapies not having paediatric indications in the United States are likely to be minimal.…”