Pediatric Patients Wait an Average of 6.5 Years Longer Than Adults to Access New Oncology Drugs

Children with cancer have to wait years before accessing new oncology drugs assessed in adults, according to a study, which found that among drugs that ultimately receive FDA approval, it takes a median of 6.5 years to go from the first clinical trial in adults to the first clinical trial in children.

With significant progress made in treating pediatric cancer over the last several decades, overall survival for children with cancer is more than 80%. However, not all pediatric patients experience favorable outcomes, and treatment-related morbidity remains high for most children treated with chemotherapy-based regimens. Currently, there are few targeted therapies approved for the treatment of pediatric patients, even with a greater understanding of pediatric cancer biology.

“Despite knowing that these agents are effective anticancer drugs, it’s taking too long to even start studying these therapies in children,” said Steven G. DuBois, MD, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and the study’s corresponding author, in a statement. “As a doctor taking care of young cancer patients, this is tremendously frustrating.”

The researchers analyzed 126 treatments first approved by the FDA between 1997 and 2017, as well as clinical trial registry data, published literature, and oncology abstracts to identify relevant clinical trials and start dates. Among the 117 non-hormonal treatments, 15 (12.8%) did not yet have a pediatric trial and 6 (5.1%) had an initial approval that included pediatric patients, including blinatumomab, clofarabine, and tisagenlecleucel. All but 1 of these 6 drugs was initially approved for the treatment of acute lymphoblastic leukemia, the most common pediatric cancer.

The median 6.5-year lag between first-in-human clinical trials and first-in-child clinical trials had a range of 0 to 27.7 years, and the median time from initial FDA approval to the first-in-child clinical trial was -0.66 years. These findings were consistent across year of initial approval, drug class, and indication.

“Some may argue that this lag is appropriate to ensure safety of a vulnerable pediatric population and to only study agents in children that are on path to FDA approval, based on activity in adults with cancer,” said DuBois. “Others may argue that this lag is too long for children with life-threatening diseases and that some agents that fail in adult indications may nevertheless prove to be important drugs for pediatric indications.”

The majority (55%) of drugs first approved during the time period were for solid tumors, while 44% were approved for hematologic malignancies. Looking at the outlier therapies with the top 5 shortest and longest lag times, the 5 drugs with the shortest duration were for hematologic malignancies, while the 5 drugs with the longest duration were approved for a range of indications.

The study also highlighted stark differences in the availability of clinical trials for adults and children. Looking at registered phase 1 and phase 2 interventional trials between the same time period, the researchers observed that 84.8% of phase 1 and 84.4% of phase 2 trials were open to adults only. Meanwhile, 14.7% of phase 1 and 15% of phase 2 trials were open to both pediatric and adult patients. Notably, just 0.43% of phase 1 and 0.6% of phase 2 trials were open to children only.

Reference:

Neel D, Shulman D, DuBois S. Timing of first-in-child trials of FDA-approved oncology drugs [published online May 2019]. Eur J Cancer. doi: 10.1016/j.ejca.2019.02.011.