Positive results with a targeted therapy for osteosarcoma, a cancer more common in young people

Osteosarcoma is a bone cancer that disproportionately affects teenagers, and outcomes for patients have changed little in decades.  Now researchers, including two OHSU Knight Cancer Institute oncologists, are reporting improved progression-free survival for patients with advanced disease receiving the drug regorafenib, a tyrosine kinase inhibitor taken in pill form.

Image: an osteosarcoma cell with DNA in blue, mitochondria in yellow and actin filaments in purple (NCI Visuals Online)“We’re really seeing a strong rationale for moving regorafenib or similar drugs forward in the treatment of osteosarcoma,” said oncologist Lara Davis, M.D., an assistant professor in the OHSU School of Medicine. She and Christopher Ryan, M.D., an OHSU professor, are principal investigators for the osteosarcoma cohort of the SARC024 clinical trial sponsored by the nonprofit Sarcoma Alliance for Research through Collaboration.

Lara Davis, M.D.

“Certainly these drugs have a role in advanced and metastatic osteosarcoma,” Davis said. “Hopefully in the future we will be able to show that they are effective to use at earlier stages in the disease.”

Each year, about 800 to 900 new cases of osteosarcoma are diagnosed in the U.S. About half of diagnosis are in children and teens. “It is a fairly rare cancer but we see quite a few patients at OHSU because most of the time these cancers get referred to sarcoma tertiary care centers,” Davis said.

For patients with localized osteosarcoma, five-year event free survival is about 70 percent following surgery and chemotherapy. If the cancer metastasizes to other organs, overall survival is about 20 percent.

The SARC024 osteosarcoma cohort enrolled subjects with advanced or metastatic tumors who had received at least one prior line of systemic therapy and who showed recent evidence of progression of disease as defined by RECIST 1.1 criteria, i.e., new disease sites or 20 percent growth of existing sites.

Christopher Ryan, M.D.

In a June 28 press release, the SARC024 investigators announced that the study goal of improving progression-free survival had been met. The study’s Data Monitoring Committee determined that “given the unequivocal and statistically significant” progression-free survival data, there was no need to enroll additional patients and that all patients receiving placebo in the osteosarcoma cohort would be offered regorafenib.

A second regorafenib clinical trial in France, the REGOBONE study, also showed a benefit for people with osteosarcoma. The median progression-free survival was 16.4 weeks with regorafenib compared with 4.1 weeks with placebo, the REGOBONE investigators reported in June at the ASCO Annual Meeting.

Davis, Ryan and co-investigators in the SARC trial are now preparing a paper to describe the osteosarcoma cohort results in more detail. “We’ll also be presenting this data at upcoming scientific meetings,” Davis said.

The SARC024 clinical trial, supported Bayer Pharmaceuticals, has four cohorts testing regorafenib in different kinds of sarcoma: liposarcoma, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma.