Blood cancers

‘Try anything’ off-label approach in childhood cancer under the microscope


Off-label use of novel drugs in paediatric oncology is inconsistently documented, results in objective response in a majority of patients but ultimately fails to impact survival, an Australian study shows.

A retrospective audit of practice at a tertiary paediatric oncology centre in Melbourne between 2010 and 2019 has identified 100 patients prescribed 133 drugs across 124 treating regimens.

The patients represented 32 unique diagnoses including rare, refractory or relapsing disease. Over half (52%) were diagnosed with a brain tumour, 31% with another solid tumour and 17% with a haematological cancer.

Patients were a relatively pre-treated population with 84% received a targeted drug at their second or greater line of treatment.

Slightly more than half (54.8%) of the drugs regimens were prescribed with curative intent and 24.2% for palliation.

“The primary reason cited explicitly by oncologists in their clinical notes for their choice to use a novel drug was genomic results identified through molecular diagnostics or inferred based on clinical diagnosis in the case of NF1 in neurofibromatosis (N = 44, 33.1%),” the study authors said.

“For seven patients, evidence from the literature or unpublished clinical trials was the primary justification for the allocation of a novel drug, while for 18 patients, novel treatments were trialed due to conventional treatment failure, but no specific evidence was cited.”

The study noted that in some specific indications, such as radiation necrosis, treatment for a bleeding syrinx, or to avoid resistance to targeted agent monotherapy, there was no explicit documented reference to the evidence for use of the selected drug in that context.

“Overall, documentation for the specific rationale behind the choice to use novel drugs varied in detail between oncologists and also between documentation prior to and following the introduction of the EMR.”

Patterns of prescription also varied between clinicians with four oncologists collectively accounting for 63.9% of the novel drug prescriptions.

The study, published in Cancer Reports, found objective responses in 73.4% of patients treated with novel drugs.

“However, more than half of the objective responses (55/91, 60.4%) did not continue past an average of 9 months. The vast majority of novel drug regimens still eventually resulted in progression of disease or no response at all, implying that these novel drugs did not definitively cure these patients.”

Other treatments including surgery, radiotherapy and bone marrow transplants around the time of novel drug use also made it difficult to attribute response to the novel drugs.

The study found overall survival was lower with novel drugs than standard of care treatment in low-grade glioma patients but similar in patients with high-grade glioma.

“The five-year OS rate for Pre-B ALL was promising; however, none of the surviving Pre-B ALL patients in this study had been evaluated for 5 years.”

“Hence, there was little evidence from this study to substantiate the benefit of novel agents for patient survival in the most prevalent diagnoses within this patient cohort. This information would clearly be significant for families’ decision-making and should be included in the informed consent process,” the study said.

Most novel drugs were funded by the hospital or compassionate access schemes.

“The results of this study indicate that while using novel drugs off-label has provided patients with some benefit, more rigorous and standardised approaches to documentation are required to fully characterise the best use of novel drugs, and to advance the ethical and clinical discussions surrounding their complex implications for patients and their families,” the study concluded.

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