A well-meaning FDA policy is a threat to pediatric cancer treatment

The medical community today faces a deceptively simple question: How quickly should we act when a child’s life is on the line? I’m a pediatric oncologist, so my answer won’t surprise you — I think we should act immediately. But a new Food and Drug Administration policy could delay things for children who need treatment now.

Many childhood cancers are still treated with intensive chemotherapies developed decades ago that leave virtually all survivors with severe or life-threatening conditions such as hearing loss, heart disease, or secondary cancers later in life. This is the unavoidable nature of these old therapies, and it’s been one of the defining paradoxes of my 20-year career in pediatric oncology: The very treatments I give children will almost always create problems for them as adults. Kids deserve better, which is why my peers and I are committed to unlocking new therapies designed specifically to cure pediatric cancers — without the collateral damage.

Today, we’re sounding the alarm. In a well-intentioned attempt to advance safer, less toxic treatments, the FDA is on the precipice of making a terrible mistake that threatens key progress in treating pediatric cancers.

An essential part of drug development is identifying the precise quantity of a drug that will help patients overcome the disease while minimizing the side effects. That process is called “dose optimization.”

Earlier this year, as part of an FDA initiative called Project Optimus, the agency proposed new industry standards that prioritize dose optimization. The new FDA standards would require trial sponsors to find the minimum dose needed for a drug to be effective before it goes to market. The laudable goal is to spare patients from the worst side effects of cancer treatments.

But here’s the problem: Project Optimus was designed with adults in mind. When applied to pediatric cancers, it threatens to slow down the very process we need to speed up: developing safer and better oncology drugs. It all comes down to basic math.

First, to accomplish Project Optimus’ goals, many more patients are required to participate in the early phases of trials. That way, researchers can compare how different groups respond to different dosing. But the 15,000 children diagnosed with cancer yearly in the U.S. represent just a fraction of the 2 million total cancer diagnoses yearly. That very small pool is the reason it can take years to enroll enough kids in a pediatric cancer trial — if the trial ever gets off the ground at all. Under the FDA’s proposal, those trials would take even longer to produce the data required for optimization.

Second, the proposal would make robust pediatric cancer trials less enticing for drugmakers. To put it frankly, the millions of adults with cancer are a lucrative market. Additional dose optimization requirements won’t deter drugmakers from spending whatever is necessary to test therapies for those patients. But federal law also requires drugmakers to study their cancer drugs in kids, which isn’t a lucrative endeavor. Kids are a relatively small group of patients covered by insurance programs that often reimburse less for therapies. Most pharmaceutical companies, especially the smaller companies with limited resources, will avoid risk and delay avoidable expenses until there is a clear path to regulatory approval and a financial return in a primary indication, most commonly in an adult cancer. Project Optimus adds unnecessary complexity, risk, and costs, and at a point that is way too early to inform efficient drug development for children. The net effect will be that drugmakers will delay the pediatric trials or discontinue development altogether.

Pediatric trials are the only way to find new and better cancer treatments. I’ve had too many conversations with desperate parents searching for any options. Never once have they told me their top priority is dose optimization.

Further slowing the already glacial pace of pediatric cancer drug development is a far greater threat to kids than unoptimized dosing. Children continue to be treated with old and poorly targeted cancer therapies, and continue to die from their cancer. This is the greatest threat we face in pediatric oncology, and it’s what federal policy should work to address. Focusing on optimization without addressing the slow pace of drug development is putting the cart before the horse. Let’s get these drugs to children as quickly as possible to see if they work and optimize the doses later.

The latest challenge posed by Project Optimus is part of a longstanding trend. When the FDA issues new policies that influence oncology drug development, children often suffer the negative consequences of fewer drugs and slower development. New policies affecting drug development, including the Project Optimus policies, should always be crafted with an eye toward the impact on children. Though the primary intent may be laudable, the unintended consequences may be severe. While the FDA’s guidance that emerged from Project Optimus is currently in “Draft” form, it’s already influencing drug development plans for children today. Once finalized — which could occur any day now — the impact will be hard to undo.

I’m urging the FDA to work with the pediatric cancer community on a dose optimization policy that works for kids — a policy that would delay optimization until there’s a clear signal that the drug may benefit children. If the FDA gets it wrong, kids and families could be stuck with the consequences for the foreseeable future. Until the FDA is willing to consider a different approach, pediatric oncologists will continue to sound the alarm.

E. Anders Kolb, M.D., is the president and CEO of The Leukemia & Lymphoma Society. He was previously chief of the Division of Hematology and Oncology of Nemours Children’s Health, Delaware Valley.