Case Study: Precision Medicine for Infantile Fibrosarcoma

When Levy was only a few months old, his parents, Gustavo and Monique, noticed swelling in the left side of his face. “It was very subtle,” Monique says. The family lives in Brazil, and they took Levy to their pediatrician, who ordered an ultrasound. The imaging revealed a very large mass in the left side of his face.

A biopsy demonstrated the mass was a sarcoma, but the specific type was difficult to classify. “We were running against time,” explains Monique, “so they started chemotherapy right away.” Levy experienced multiple side effects of chemotherapy, including febrile neutropenia and sepsis.

A chemotherapy-resistant tumor

Unfortunately, despite trying multiple empiric chemotherapy regimens for sarcoma, the tumor remained unresectable. Levy continued to experience multiple side effects including repeated episodes of febrile neutropenia — and his specific type of sarcoma remained unknown. “It was not shrinking the tumor,” says Monique. “I thought, ‘We can’t keep doing the same thing.’”

In May 2018, it was suggested that Levy be seen at a cancer center in Houston, Texas. Once there, 11-month-old Levy was diagnosed with infantile fibrosarcoma. This is a very rare, fast-growing tumor with a specific genetic change called an NTRK gene fusion that drives cancer-cell growth. Based on this information, Levy qualified for a clinical trial being conducted in Dallas led by Theodore Laetsch, MD. The trial was was for an oral drug called larotrectinib, which blocks the oncogenic TRK fusion protein and stops cancer-cell growth. Dr. Laetsch is the international lead investigator for the clinical trial of larotrectinib in children, and he has since come to Children's Hospital of Philadelphia’s (CHOP) to launch and lead the Very Rare Malignant Tumors Program and the Center for Precision Medicine for High-Risk Pediatric Cancer.

A dramatic response to the therapy

Levy, pictured with his parents and brother. “Our lives changed after the medication,” says Monique. “All the complications of chemo — everything changed. Within one month, the tumor began shrinking. After three months, it shrunk 70%.” The family traveled from Brazil to Dallas every month until the beginning of the pandemic, and then visits were handled through video calls.

In September 2020, Dr. Laetsch joined the Division of Oncology at CHOP. Levy’s family followed Dr. Laetsch to CHOP. Now 5 years old, Levy shows how some children with rare and complex tumors respond to treatment based on specific genetic targets within the individual patient’s tumor.

Data from the trial Levy took part in was combined with data from a separate adult study and led to FDA approval of larotrectinib in children and adults with solid tumors that have NTRK gene fusions and don’t respond to standard therapy or for whom no acceptable therapy is available — the first time a cancer treatment was granted initial FDA approval based on the presence of a genetic mutation regardless of the type of tumor in which it occurs, so-called histology agnostic approval. This was an important step toward fulfilling the promise of safer, more effective cancer treatments with fewer side effects.

Building on this progress, through the Children’s Oncology Group (COG), Dr. Laetsch now leads a clinical trial testing whether larotrectinib can be used instead of chemotherapy — an approach that may spare patients the side effects that Levy initially experienced. One important question that remains with precision therapies like larotrectinib is how long patients must continue these treatments. Dr. Laetsch presented initial data at the 2022 CTOS Annual Meeting suggesting that some patients can maintain remission off treatment, and he is currently studying this approach through the COG study. Levy stopped taking the drug in June 2022 and is being followed to see if he can maintain his remission off treatment.