twitter Tweet

Targeted therapy stops a rare, joint-destroying tumor

OHSU cancer researcher helped lead study finding first effective drug therapy for tenosynovial giant cell tumor, or TGCT
Brian Matekovich riding a motorcycle
Brian Matekovich had lived for years with pain and inflammation from a rare type of tumor in his knee, but found rapid relief with his first dose of pexidartinib. The drug is the first to reduce tumor size and improve symptoms for those with TGCT and has been approved by the FDA. (OHSU/Kristyna Wentz-Graff)

Brian Matekovich was in his late 30s when he began experiencing inexplicable pain and swelling in his right knee. It took years to get a correct diagnosis: tenosynovial giant cell tumor, or TGCT, a rare type of tumor that slowly destroys joint cartilage and bone. Physicians treated the pain and inflammation but could do nothing to stop the damage.

Over time, Matekovich said his knee swelled to the size of a cabbage and became so locked up he could not walk up or down stairs. “The pain was pretty intense actually,” said the 49-year-old, who found his way to OHSU, where he enrolled in a clinical trial of an experimental drug called pexidartinib. Taken in pill form, it precisely targets a signaling path that has gone awry within cells to enable the disease.

For Matekovich, the drug’s effect was rapid. “After the first dose, my knee started feeling much, much better,” he said. “After the first month, I was the best I’d felt in years. Today, the swelling is essentially gone. My right knee looks like my left knee.”

Pexidartinib, which will be sold as Turalio, is the first drug shown to reduce tumor size and improve symptoms and functional outcomes in people with TGCT. Made by Daiichi Sankyo, the drug has just received approval from the U.S. Food and Drug Administration.

Christopher Ryan, sitting and looking directly at a camera
Christopher Ryan, M.D., professor in the OHSU School of Medicine, co-authored the journal article describing the results of the multi-center study. Ryan enrolled and cared for Matekovich and other clinical trial participants at the OHSU Knight Cancer Institute. (OHSU/Kristyna Wentz-Graff)

“It is a drug that works amazingly well,” said Christopher Ryan, M.D., who co-authored the journal article describing the results of the multi-center study. “It will require careful management, however, because it can have side effects,” he said. Ryan enrolled and cared for Matekovich and other clinical trial participants at the OHSU Knight Cancer Institute. He is a professor of medicine (hematology and medical oncology) in the OHSU School of Medicine.

Ryan said the drug fills a longstanding unmet need. Surgery can help some people but relapse rates are high and repeat surgeries largely futile. Many, including Matekovich, are not good candidates for surgery because the inflammation and abnormal growth are spread diffusely around the joint. “Until now, we haven’t had much to offer these patients,” Ryan said.

The clinical trial enrolled 120 people with TGCT untreatable by surgery. They were randomly assigned to receive either pexidartinib or an inactive placebo, without knowing which. After six months, those in the placebo group were switched to the active drug. The study found that 39% of patients taking pexidartinib responded to treatment, while none getting the placebo responded. Patient-reported measures of physical function and stiffness improved significantly with pexidartinib, Ryan and co-authors reported in June in The Lancet medical journal.

Hair color changes and fatigue were the most common side effects, but there was also a rare occurrence of liver toxicity serious enough that the study’s data monitoring committee stopped enrollment six patients short of the study’s target.

To date, there have been two reported cases of irreversible liver injury among the 768 people who have taken the drug. One patient died with advanced cancer and ongoing liver toxicity, and one patient required a liver transplant, the company reported.

The risk of liver damage will require some precautions, especially because this type of tumor is not life-threatening, Ryan said.

The FDA approval of Turalio stipulates that the drug’s packaging includes a boxed warning about liver toxicity. And the drug will be available only through a restricted program (called a Risk Evaluation and Mitigation Strategy or REMS) so that only certified healthcare providers may prescribe it.

Brian Matekovich, sitting on his motorcycle and looking at camera
Matekovich has experienced a few side effects from the drug. All his hair turned white, pigmentation changes made his skin very sensitive to sunlight and he lost his sense of taste for a few months. But he says all things considered, his side effects are tolerable. (OHSU/Kristyna Wentz-Graff)

Matekovich believes he received the placebo, not the active drug, during his first six months in the study. It became obvious at six months, he said, when the study protocol switched placebo recipients to the active drug. Matekovich said his knee pain suddenly stopped and the swelling began to shrink. He also experienced one of the most common side effects: “All the hair on my body turned white,” he said. The pigmentation changes made his skin very sensitive to sunlight. He also lost his sense of taste for a few months. Matekovich continues to take two pills, twice a day as a participant in the clinical trial. He has not had liver problems.

All things considered, Matekovich said his side effects are tolerable. The disabling disease was interfering with his ability to do his job as a draftsman for a commercial carpentry business. It had forced him to give up motorcycling and other activities. Pain was robbing him of sleep every night. These days he’s sleeping soundly and active at work and at play. “I can walk again,” he said. “I can walk for miles. I can go back to doing all the things I like to do.”

The clinical trial was funded by Daiichi Sankyo.

Previous Story New computational method could advance precision medicine Next Story Better, longer-lasting flu vaccine to be developed at OHSU
Facebook Twitter LinkedIn YouTube Instagram OHSU Braille services OHSU sign language services OHSU interpreter services