Sarcoma Studies Fuel New Model for Childhood Cancer Research

Children are more likely to survive cancer than ever before. Yet stubborn challenges undermine care for pediatric patients with tumors that occur infrequently in adults. These rare cancers are vastly understudied.

Sarcomas comprise just 1% of adult cancers but approximately 10% of youth malignancies, with 850 to 900 pediatric soft-tissue tumor diagnoses in the U.S. annually. Many children are diagnosed with advanced or recurring disease, and the few effective therapies carry a litany of toxic side effects. Five-year survival for pediatric patients with recurrent sarcomas can be as low as 13%.

An expanding movement to integrate sarcoma research across ages gives fresh hope for young, critically ill patients. Groundbreaking clinical trials led by Cedars-Sinai Guerin Children’s Pediatric Hematology and Oncology Director Leo Mascarenhas, MD, MS, explore novel therapies in children, adolescents and young adults.

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“These are incredibly rare cancers. When we expand the group of patients we are investigating, we draw conclusions much sooner and spread the impact over a broader population,” Mascarenhas said.

Cedars-Sinai’s approach is reaping benefits for children with sarcomas, who can access potentially lifesaving medicines earlier than ever before. On average, adult patients gain access to newly approved cancer treatment regimens 6.5 years before they are available to pediatric patients, according to a 2019 analysis of federally approved oncology drugs.

The most crucial lesson in implementing this model is that it is actually possible and feasible to conduct oncology trials for different age groups side by side.

Promise in Pediatric Cancer Innovation

Across multiple Guerin Children’s sarcoma trials, Mascarenhas is aiming to realize the potential of immunotherapy and cell therapy advances.

Investigators are researching a novel sarcoma drug, PEEL-224, in children, teens and adults up to age 40. The medicine inhibits topoisomerase, an enzyme that untangles DNA strands and is central to tumor cell replication.

Another study tests—for the first time—a bispecific T-cell engager (BiTE), xaluritamig, for treating Ewing sarcoma in young patients up to adulthood. The targeted drug has shown promise in prostate cancer and is similar to blinatumomab, which targets a different protein and has transformed childhood leukemia outcomes, halving leukemia relapse in the bone marrow and boosting survival to more than 90%.

“We know this immunity lasts for along time,” he said. “If you figure out a way to get the immune system to recognize cancer, that will likely prevent relapses down the line because of stored memory within the immune system.”

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Mascarenhas’ collaborative investigations secured the first joint therapeutic approval for a rare type of sarcoma in pediatric and adult patients. Their studies on larotrectinib, another targeted therapy now approved for use in patients with a specific gene fusion, established a foundation of evidence for the approach.

“The most crucial lesson in implementing this model,” he said, “is that it is possible and feasible to conduct oncology trials for different age groups side by side.”