In a study reported in the Journal of Clinical Oncology, Sabnis et al analyzed characteristics of genomically targeted single-patient use requests for investigational agents for the treatment of pediatric cancers. These requests were made from pediatric cancer programs over a 5-year period.

As noted by the investigators, “The U.S. Food and Drug Administration (FDA) expanded access program uses a single-patient use mechanism to provide patient access to investigational agents in situations where no satisfactory or comparable therapy is available. Genomic profiling of de novo and relapsed or refractory childhood cancer has led to increased identification of new drug targets in the last decade.”

The study included data on all genomically targeted therapeutic single-patient use requests obtained between January 2014 and June 2019 at four large U.S. pediatric cancer programs. 

Key Findings

A total of 45 single-patient use requests for 44 patients were identified. Patients had a median age of 8 years. Among requests, 18 were for central nervous system tumors, 20 were for solid tumors, and 7 were for hematologic malignancies.

The most common reasons for single-patient use requests were lack of availability of a clinical trial (64.4%) and ineligibility for a clinical trial (28.9%).

Median time from FDA submission to approval was 3 days (range = 0–12 days). Median time from institutional review board submission to approval was 5 days (range = 0–50 days).

The median duration of single-patient use therapy was 216 days (range = 2–1,832 days). Among 38 evaluable patients, an objective response was observed in 15 (39.5%), with complete response in 3 (7.9%). An additional seven patients (18.4%) had stable disease.

Of the three patients with a complete response, one had a hematologic malignancy and two had solid tumors; the duration of therapy in these patients was 216, 531, and 1,085 days, respectively. Of the 12 patients with a partial response, 9 had solid tumors and 3 had central nervous system tumors; the median duration of treatment in these patients was 620 days (range = 90–1,832 days). The most common reasons for discontinuation of single-patient use therapy were disease progression (66.7%) and toxicity (13.3%).

With regard to specific genomic alterations, BRAF (n = 6) and FGFR1 mutations (n = 5) were the most common among 18 patients with central nervous system tumors. Mutations in 20 patients with solid tumors included NF1 in three patients, and SMARCB1, RET, NUTM1, NTRK3, MDM2, and ALK in two patients each. Each of seven patients with hematologic malignancies had a unique mutation. Objective responses were observed across eight different gene targets. 

The investigators concluded, “Single-patient use requests remain an important mechanism for pediatric access to genomically targeted agents given the limited availability of targeted clinical trials for children with high-risk neoplasms. Furthermore, this subset of single-patient use requests resulted in a substantial number of objective tumor responses. The development of a multi-institutional data registry of single-patient use requests may enable systematic review of toxicity and clinical outcomes and provide evidence-based access to new drugs in rare pediatric cancers.”

Himalee S. Sabnis, MD, MSc, of The Aflac Cancer & Blood Disorders Center, Children’s Healthcare of Atlanta, Emory University, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.