Drug Discovery a Challenge for Pediatric Cancers

Published in Promise & Progress - Promise & Progress 2018

Pediatric cancer expert Patrick Brown recognizes the promise of new drug discovery and development in making progress against cancer, and it’s at the heart of his frustration. Brown, who has taken FLT3 inhibitors and other investigational drugs to pediatric leukemia patients, says children are often the last to benefit from new drugs for many reasons. “Access to drugs and the ability to explore them are the biggest barriers to changing standard of care for pediatric patients,” says Brown. Even when Kimmel Cancer Center researchers make a drug discovery, they typically can only take it so far. “We can’t mass-produce drugs, so we usually rely on drug companies to provide drugs for clinical trials,” says Brown. The much smaller number of patients with pediatric cancers compared to adult cancers and the risk of something going wrong with a drug being tested in children can make pharmaceutical companies reluctant to provide drugs.

This has hindered access to promising new drugs greatly and slowed progress against pediatric cancers, Brown says. For new FDA-approved drugs, it is possible to get them for study in pediatric patients by purchasing the commercial drugs outright, but costs can vary from $1 million to many millions, and these costs are not typically covered by federal research grants. There are a few federal laws meant to encourage drug companies to invest in pediatric clinical trials, but Brown says they are largely not very effective. In pediatric oncology, large, multi-institutional studies are the only way to include enough patients to accurately evaluate a new drug, but drug companies are not often willing to support these studies. “Getting therapies for individual patients in small studies is fine, but if we can’t do a large-enough trial to demonstrate survival benefit over standard of care, we can’t change standard of care,” says Brown. “We are constantly pitching ideas, and experts agree drugs should be tested in kids, but frequently we can’t get the drug for our studies.”

Most large trials are done collaboratively with pediatric oncologists from the 220 institutions that make up the Children’s Oncology Group. The group recently proposed a study to look at an immunotherapy drug as upfront treatment for acute lymphocytic leukemia (ALL). “We are completely at the mercy of the drug company as to whether or not it will provide the drug for this study,” says Brown. “If it says no, which is the most likely answer, the study doesn’t happen. Immunotherapy could be a game changer for kids with ALL, and we’re struggling to get the drugs in a timely way. That’s very frustrating for us.” Brown says these large studies are really the only way they can begin to move pediatric oncology treatment away from the toxic chemotherapies that can have devastating latent effects in children to the new, short and long-term targeted therapies that are already benefiting adult patients.

Brown and his colleagues try to work with drug companies to form clinical research agreements that include providing drugs for pediatric studies. But, Brown says, “There is not much financial upside for companies to give their drugs away for pediatric clinical trials when they could otherwise sell them.” Still, they keep trying, and occasionally they’re successful. Amgen is providing a drug and significant funding to support a clinical trial comparing chemotherapy alone to a combination of chemotherapy and immunotherapy for ALL. “If successful, this study will change standard of care for ALL,” says Brown. “There might be some financial payoff for them because ALL is the most common pediatric cancer, but mostly this an altruistic venture on their part.”

Celgene is another example. The company is providing one of its drugs, azacytidine, for an infant leukemia study. Infant leukemia is an extremely rare but very deadly cancer badly in need of new drugs, but Brown says it’s very difficult to get companies to provide drugs for studies. Brown says one solution would be an independent funding source that could purchase FDA-approved drugs and provide them for pediatric studies. Kimmel Cancer Center Director William Nelson will explore such a mechanism as part of the Kimmel Cancer Center's drug discovery and development program. “We all have to be invested in doing better for kids,” says Brown. “If there is a way to treat patients and get better cure rates with lower toxicities, we should be doing the studies that make these treatments available to pediatric cancer patients.