Pediatric patients with recurring osteosarcoma have not seen a successful new drug treatment in nearly 30 years. With a survival rate of less than 20 percent, these patients are now hoping the new drug avelumab will be an answer for children ages 12 and up with recurring or progressive osteosarcoma.
Michael Bishop, MD, at St. Jude Children’s Research Hospital is leading a phase two study that began in January to test avelumab in adolescent and young adult patients 12 years of age and older. Avelumab is an immune checkpoint inhibitor that targets cancers by blocking PD-L1 (programmed death ligand-1). It’s an anti-PD-L1 monoclonal antibody, inhibiting interactions between PD-1 expressed on T cells and PD-L1 on cancer cells, allowing the T cells to activate and target tumor cells.
Additionally, in contrast to other available PD-1/PD-L1 inhibitors, avelumab has the ability to induce antibody-dependent cellular cytotoxicity (ADCC). PD-L1 is a protein found on normal cells as well as some cancer cells that serves as a “lock” for the “key” of PD-1. When the protein PD-1 binds to PD-L1, it signals to the immune T cells that this cell is normal, so the immune system does not attack.
Per the American Cancer Society, PD-1 inhibitors are being used to treat melanoma, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma. Whereas PD-L1 inhibitors like avelumab, atezolizumab or durvalumab are currently being prescribed for treating bladder cancer, non-small cell lung cancer and Merkel cell skin cancer.
The success of immune checkpoint inhibitors in adults with various cancers with high rates of mutations “provided some interest for us in treating our patients” said Bishop about the study at St. Jude, as osteosarcoma is one of the most highly mutated pediatric tumors. This new class of treatment has shown promise in adults especially when combined with other checkpoint inhibitors with different targets such as CTLA-4. The use of immune checkpoint inhibitors is relatively new in pediatric oncology said Bishop, and studies like the avelumab phase two research study provide a window into the possibilities for children with recurring osteosarcoma.
But, the immune checkpoint inhibitors can lead to the immune system attacking non-cancerous cells and serious side effects like nausea or issues with organs like the lungs. Even though the drug is approved by the FDA for treating adults with certain cancers, there are less data on toxicity in children and quality of life concerns. Bishop is monitoring the quality of life and side effects of avelumab in the trial at St. Jude by having patients complete questionnaires about physical and emotional wellbeing throughout the study.
The trial also includes several correlative biology studies developed in conjunction with St. Jude Immunology members. These include looking at expression of certain markers on tumor cells, as well as markers of “exhaustion” on T cells related to chronic antigen exposure and the likelihood of tumors to respond based on their presence. Bishop hopes that these studies will improve our understanding of the use of immune checkpoint inhibitors by making “novel insights on how the interplay between tumor and immune system impact the ability to generate a response to these types of therapies.”
Physicians at St. Jude are studying the response of the tumors and the length of time patients are receiving the drug without tumor growth. For the trial, St. Jude is studying patients ages 12 or older with measurable recurrent or progressive osteosarcoma. St. Jude is hoping to recruit 32 patients in total over the course of this three-year trial. Every two weeks, patients are treated with avelumab and evaluated by imaging at 8 weeks, 16 weeks and then every 12 weeks following.
Currently, St. Jude is the only hospital testing avelumab in adolescents and young adults, but Texas Children’s Hospital, Memorial Sloan Kettering and Children’s Hospital of Los Angeles will be opening this trial soon.
While it’s too early to tell if the immune checkpoint inhibitor avelumab will be useful for children with osteosarcoma and potentially other cancers, it is hopeful to have a potential treatment for the recurrence of the most common type of pediatric bone cancer.
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