The University of Oklahoma Health Sciences Researcher Part of Study Leading to New Treatment for Rare Cancer

OU Health Stephenson Cancer Center at the University of Oklahoma Health Sciences researcher Abdul Rafeh Naqash, M.D., serves as co-author of a study published recently in the New England Journal of Medicine that details the success of a newly approved drug for treating a rare form of sarcoma. The drug is a type of immunotherapy, which prompts the body’s immune system to recognize and fight cancer cells.

In December 2022, the Food and Drug Administration approved the drug atezolizumab for the treatment of alveolar soft part sarcoma, a cancer that starts in different types of soft tissue, such as muscle, fat or nerves. The FDA approved the drug after the success of the Phase II clinical trial described in the publication. The Division of Cancer Treatment and Diagnosis at the National Cancer Institute conducted the study, which was led by Alice P. Chen, M.D., and Elad Sharon, M.D., MPH. Naqash assisted with the study while he was a fellow at the NCI two years ago and continues researching treatments for alveolar soft part sarcoma at the OU Health Sciences Center.

The drug approval addresses the urgent need for a means of treating alveolar soft part sarcoma, an aggressive cancer with a poor survival rate. Alveolar soft part sarcoma primarily occurs in adolescents and young adults and is rare, with a global incidence of less than 1 person per 1 million people. No good treatments exist, and only 20% to 46% of people diagnosed with alveolar soft part sarcoma survive five years after learning they have the disease.

“Until now, no treatments were available that could lead to significant improvement in people with alveolar soft part sarcoma. This is also the first full approval of an immunotherapy drug for a rare type of sarcoma,” said Naqash, an assistant professor in the OU College of Medicine and a hematologist oncologist at Stephenson Cancer Center.

In the study, tumors shrank in 37% of participants who received the drug; in one person, the drug appeared to eliminate the tumor. Participants continued to respond to the drug for approximately two years without their cancer growing or spreading. Researchers found no unusual side effects to the drug.

Naqash continues to study sarcoma treatments using a variety of approaches. In one area of focus, he analyzes biopsy samples from people with alveolar soft part sarcoma to look for methods of predicting why some patients respond to treatment and others don’t. He is collaborating on a portion of that research with Wei Chen, Ph.D., the Stephenson Chair and Professor of Biomedical Engineering in the Gallogly College of Engineering on OU’s Norman campus. Last year, Naqash received an Impact Award from the Hope Foundation for Cancer Research, which is part of the Southwest Oncology Group (SWOG) Cancer Research Network, to fund his research.

He also continues to study another interesting finding from the NCI trial. Study participants who responded to the immunotherapy drug did so even if they had low levels of a protein called PD-L1 on their cancer cells. PD-L1 is normally found on certain healthy cells and helps to stop immune system cells (T cells) from attacking healthy cells in the body. If cancer cells have high amounts of PD-L1, they can “turn off” the immune system’s T cells so they can’t attack the cancer. If that is the case, immunotherapy drugs may be used to prevent PD-L1 from putting the brake on T cells, which frees them to fight cancer. However, in this study, the amount of PD-L1 did not appear to play a role in whether participants responded to the drug, suggesting that other immune mechanisms may be at play.

In October, Naqash will give a presentation at the European Society of Medical Oncology meeting in Spain. His remarks will focus on a unique gene fusion — a hybrid gene that forms from two previously independent genes — that occurs in alveolar soft part sarcoma. Naqash is working with the company Caris Life Sciences for that portion of his research.

“This type of research is important because rare tumors account for 20% to 25% of total cancers, yet not a lot of emphasis is given to rare tumors,” Naqash said. “Clinical trials have difficulty enrolling patients and few pharmaceutical companies are interested in rare tumors. This is an area of unmet need.”

For more information about Naqash’s research, email AbdulRafeh-Naqash@ouhsc.edu. To read the recent publication in the New England Journal of Medicine, titled “Atezolizumab in Alveolar Soft PartSarcoma,” visit the journal’s website at nejm.org.