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An uptick in new drugs and clinical trials for sarcoma

December 6, 2016

Vanderbilt-Ingram Cancer Center (VICC) has launched seven clinical trials for sarcoma drugs since 2015, with three of those opening up for participants as recently as August 2016.

“We are in great need of novel therapies,” said Scott C. Borinstein, M.D., Ph.D., director of the Pediatric Sarcoma Program at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

For decades, the treatment regimen for the more than 80 subtypes of sarcoma has been surgery, radiation and chemotherapy.

“Surgery is imperative for a cure,” said Vicki Keedy, M.D., MSCI, clinical director of The Vanderbilt Sarcoma Center. “Chemotherapy and radiation alone will not cure adult soft tissue sarcomas, and the correct surgery is important as well. Some pediatric sarcomas respond well with chemo/radiation without surgery.”

Until recent years, the same chemotherapy drugs were used regardless of the sarcoma subtype — in most cases doxorubicin, a drug that has been around for four decades.

In October 2016, the U.S. Food and Drug Administration approved olaratumab, the first new therapy for the initial treatment of soft tissue sarcoma since doxorubicin’s approval more than 40 years ago. Olaratumab, which is an antibody that blocks a receptor that when stimulated promotes tumor growth, is approved in combination with doxorubicin.

In October 2015 the FDA approved trabectedin for two subtypes, liposarcoma and leimyosarcoma, giving patients who had not responded to older drugs another chemotherapy option. In January 2016, the agency approved another chemotherapy, eribulin, for liposarcoma that can’t be surgically removed or has metastasized.

“Chemotherapy remains pretty controversial,” Keedy said. “In the curative post-surgery setting, we haven’t identified who benefits from chemotherapy and who doesn’t. In the metastatic setting, in the non-curable patient, chemotherapy clearly has a role for palliation over time.”

Generally, patients with pediatric sarcomas respond better to chemotherapy than patients with adult-type sarcomas.

The fact that sarcoma cancers are rare diseases hinders research. Most research is limited to randomized clinical trials across cancer centers such as VICC that specialize in sarcoma. VICC is a member of the Sarcoma Alliance for Research Through Collaboration (SARC).

Keedy has advocated for more research at the preclinical stage.

“I applaud the sponsors who put their resources into large randomized studies of such a rare disease; however, we must push for increased funding of preclinical research to identify compounds,” she wrote in an editorial for Oncology Journal.

Keedy and Borinstein are both directing clinical trials of potential new drug therapies.

“Immunotherapies are being investigated in sarcomas, but there have not been the dramatic amazing responses that we have seen in such cancers as melanoma or lung cancer,” Borinstein said. “But they are being intensely investigated. I’m hopeful we are going to see responses, and we can figure out ways to use these drugs.”

In one early clinical trial of the immunotherapy pembrolizumab, 33 percent of patients with undifferentiated plesomorphic sarcoma and

dedifferentiated liposarcoma (two sarcoma subtypes) had a reduction in tumor size, according to a preliminary report from researchers at the June 2016 meeting of the American Society of Clinical Oncology.

Elizabeth J. Davis, M.D., who joined VICC in August from the University of Michigan Comprehensive Cancer Center, was an investigator on that study. One of her patients was an exceptional responder.

“She had almost a complete response to this drug, which is kind of amazing because she is 26 years old and had extensive disease all over her body,” Davis said. “It is unclear why she responded so dramatically.”

The drugmaker is doing further study on her histology in an attempt to identify the reason, Davis said. A final report of this ongoing clinical trial has not yet been published in a medical journal.