Recent advances have resulted in highly effective "tissue-agnostic" drugs that treat cancers based on their molecular markers rather than their tissue of origin, but very few of these drugs are approved for use in children. In an opinion paper publishing June 5 in the Cell Press journal Trends in Cancer, oncologists call for "ag(e)nostic" cancer treatments: drugs that are both tissue agnostic and approved for cancer patients of all ages.
"Cancer treatment in children is a huge unmet need. These drugs are extremely effective, and we want to see children have access to them," says senior author Razelle Kurzrock, an oncologist at the Medical College of Wisconsin. "Personally, I think that all drugs should be age agnostic."
In the past, cancers were diagnosed and treated based on their tissue of origin, but modern precision cancer treatments target specific molecular abnormalities either directly or by flagging them for the immune system. Since cancers from different tissues sometimes use the same molecular abnormalities to grow and evade the immune system, the same drugs can be used tissue-agnostically to treat various cancers. And because of their targeted nature, precision treatments often have fewer side effects compared to traditional cancer treatments.
"Cancer is driven by underlying genomic drivers; it's not driven by whether the cancer comes from the colon or the breast," says Kurzrock. "Precision treatments are like smart bombs—they give therapy that is precisely targeted to the abnormality in the cancer."
However, very few tissue-agnostic precision drugs are approved for use in children. The researchers note that as of June 2024, 144 out of 187 precision cancer treatments were only FDA-approved for adults. Similar patterns are present in the European Union and Japan.
"Only three cancer drugs are approved across all ages," says Kurzrock. "There are another four that are only approved for children in certain age groups, for example, age 12 and up or age 6 and up. But that still means that if you're a 10-year-old and you have a tumor, insurance doesn't have to pay for your drug if it's only approved for use in 12-year-olds."
The researchers say that there are several historical reasons why fewer precision treatments have been approved for children.
"By nature, children are defined as a more vulnerable population, and they can't give their own consent," says author Matthew Kudek, a pediatric oncologist at the Medical College of Wisconsin. "Another issue is that pediatric oncology doesn't have the same potential for revenue generation as adult cancers do because childhood cancer as a whole is a rare thing, so each cancer inside of that is even rarer."
However, from a scientific and clinical standpoint, the researchers argue that there's no reason why these drugs shouldn't be approved for children.
"Children actually tolerate drugs much better than adults, especially older adults," says Kurzrock. "If you can treat an 80-year-old with a drug, you should be able to treat a 2-year-old. They're much more adaptable and they experience much fewer side effects."
Although the rarity of childhood cancer means that it is nearly impossible to find adequate patients to run pediatric clinical trials, the researchers say that these drugs could be approved for age-agnostic use by other means, for example, by analyzing electronic health record data.
"If we can understand a medicine's absorption and clearance rates, and we know what dose might be needed to kill cancer cells, we can use those tools and data to make a compelling case that it is both safe and effective in different populations," says Kudek. "Moving forward, age-agnostic approvals should be the norm for precision cancer treatments rather than an exception to the rule."
