Targeting osteosarcoma, a cancer more common in young people

Knight Cancer researchers describe positive results with the drug regorafenib.

Osteosarcoma is a bone cancer that disproportionately affects teenagers, and despite substantial efforts, outcomes for patients have not changed much in 30 years. But last year, two groups of researchers reported positive results with the drug regorafenib in those with relapsed or metastatic osteosarcoma, for which no other therapies have proven to be effective.

This week, Lara Davis, M.D., an assistant professor in the OHSU School of Medicine, is the first author of a new paper in the Journal of Clinical Oncology presenting detailed results from one of the regorafenib trials. Davis and Christopher Ryan, M.D., an OHSU professor, are principal investigators for the osteosarcoma cohort of the SARC024 study sponsored by the nonprofit Sarcoma Alliance for Research through Collaboration.

Regorafenib, taken in pill form, is an inhibitor that blocks the activity of several protein kinases involved in tumor formation and progression. It is approved by the Food and Drug Administration to treat metastatic colorectal cancer, liver cancer and gastrointestinal stromal tumors.

The SARCO24 osteosarcoma trial 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.

In a press release last June, SARC announced that the study was stopped early, having met its goal of improving progression-free survival, that is, the duration of months lived without worsening of the disease.

Davis and co-authors now report that median progression-free survival was roughly doubled with regorafenib: 3.6 months versus 1.7 months in the group initially assigned randomly to receive a placebo. A total of 42 subjects participated in the trial. Ten of the 20 assigned to the placebo group crossed over to the active drug when their cancer progressed.

In the context of the crossover design, there was no statistically significant difference in overall survival, the authors said. Fourteen of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 adverse events attributed to treatment, including skin reactions, gastrointestinal disorders, and hypertension.

The investigators concluded that regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma. They said studies of combination regimens that include regorafenib are a natural next step in the development of new treatments for people with osteosarcoma.

Further reading:

Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma by Lara E. Davis, Vanessa Bolejack, Christopher W. Ryan, Kristen N. Ganjoo, Elizabeth T. Loggers, Sant Chawla, Mark Agulnik, Michael B. Livingston, Damon Reed, Vicky Keedy, Daniel Rushing, Scott Okuno, Denise K. Reinke, Richard F. Riedel, Steven Attia, Leo Mascarenhas, and Robert G. Maki. Journal of Clinical Oncology (April 23, 2019)