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Oral Drug Combination Shows Benefit for Adults with Ependymoma

, by Kendall Morgan, NCI-CONNECT Contributor

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Learn how results from the first prospective clinical trial for adults with ependymoma led to a change in treatment guidelines, offering hope to control the disease and improve symptoms.

When an adult is first diagnosed with the rare brain and spine tumor known as an ependymoma, doctors often treat it with surgery followed by radiation. However, until recently, if the tumor came back there were no standard treatment options. That’s now changed, thanks to results from the first prospective clinical trial for adults with ependymoma, which—in another first—showed benefits of a combination regimen including a targeted drug and chemotherapy.

“We did see some tumors shrink,” said Mark Gilbert, M.D., lead investigator and chief of the NCI Center for Cancer Research's Neuro-Oncology Branch. “For most patients, the benefit was measured by preventing tumor growth. Importantly—because we included assessment of patients' symptoms—the trial also showed the impact the treatment had on their quality of life. Even in the absence of tumor shrinkage, there was improvement in symptoms.”

Earlier ependymoma trials had been unsuccessful due to the rarity of the cancer and associated challenges in recruiting patients. “The biggest barrier in studying rare diseases is that they are rare,” Dr. Gilbert said. The recent findings, published in Neuro-Oncology, were made possible by the Collaborative Ependymoma Research Network (CERN) Foundation and their referral program. The foundation was established in 2006 to improve the care and outcome of people with ependymoma.

Trial Design and Outcomes

Dr. Gilbert and colleagues enrolled 50 patients with recurrent ependymoma from grade 1 to 3 into the phase 2 trial. Trial participants received a combination treatment of two oral agents, the chemotherapy drug temozolomide (TMZ) together with daily lapatinib.

The researchers chose TMZ because it crosses the blood-brainbarrier and has an established track record for safety and efficacy in treating other brain tumors. They chose lapatinib, used to treat advanced HER2-positive breast cancer, because it targets mutations in the genes EGFR and HER2, both of which are found in many cases of ependymoma. While they were already in use for treating brain and breast cancer, the two drugs had never before been used in combination. The fact that both drugs could be taken orally by patients at home also was key to their selection and the trial’s success.

“We needed a regimen that was easy to administer,” Dr. Gilbert said. “When you think about enrolling patients in a trial, you have to think about logistics and practicality. If patients have to be seen every week, that’s not easy if they are far away. Because this disease is rare, we’re looking at a small population of patients living all across the United States.”

The combination treatment was generally well tolerated. In many cases, it also worked. In half of the study’s participants, the tumor stopped growing for 7.8 months or more. At six months, 55 percent of patients in the study had survived with no evidence of progression. After a year, 38 percent of individuals in the study survived with tumors that remained stable. Eight patients in the study (16 percent) had their tumors shrink, including two that showed a complete response and six others that had a partial response.

Terri Armstrong, Ph.D., deputy chief of the Neuro-Oncology Branch who served as the patient-reported outcomes chair of this study, focused on understanding the clinical impact of treatment. The researchers used various instruments developed by Dr. Armstrong and colleagues to collect information from trial participants about the symptoms they were experiencing. Participants also reported how much symptoms were interfering with daily activities, mood, and work. While the treatment wasn’t without side effects, most patients in the study reported a reduction in moderate-to-severe pain and other disease-related symptoms while taking TMZ and lapatinib. Those improvements in symptoms, even without tumor shrinkage, came as a welcome surprise, according to the researchers.

“We envisioned that patients with controlled disease would maintain whatever symptom burden they had to start with but wouldn’t get worse,” Dr. Gilbert said. “So, to actually see improvement in function and symptoms was really incredible.”

Advancing Treatment

While the treatment isn’t approved for recurrent ependymoma by the Food and Drug Administration (FDA), the trial results have already led to a change in treatment guidelines from the National Comprehensive Cancer Network (NCCN). This means that adults with recurrent ependymoma can now be treated with this combination as a standard of care, offering hope to control the disease and improve symptoms.

“The take home message is that we were able to launch and complete this clinical trial,” Dr. Gilbert said. “We were excited that it worked. It now stands as a treatment patients can get as we continue to look for new treatments for ependymoma and other rare cancers. The most essential component is patient enrollment and participation. If people don’t enroll, we can't do the trial. If we can’t do the trial, we don’t make advancements.”

He recommends that anyone with cancer—especially if it’s a rare or otherwise hard-to-treat cancer—consider participating in ongoing clinical trials. That’s especially important, he says, when there is no proven treatment available. 

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