New Desmoid Tumor Treatment Improves Results in Sarcoma Patients

Sarcoma treatment
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Dana Avellino, now 36, initially thought a lump she felt in the summer of 2018 was due to her recent cesarean section. At the time, her younger daughter was just two months old. Her doctors advised that she visit Memorial Sloan Kettering Cancer Center (MSK), which is renowned internationally for its expertise in treating sarcomas after a biopsy indicated that the lump was a sarcoma, a form of tumor that affects the body’s soft tissues.
Dana’s MSK physician, Mrinal Gounder, MD, a sarcoma specialist, informed her about a clinical trial investigating an experimental targeted medication called nirogacestat after she experienced severe side effects from earlier therapies. About three years have passed since Dana started taking the medication.

Her tumor, a rare, noncancerous subtype of sarcoma called a desmoid tumor, has shrunk so much that she can hardly feel it anymore.

“When I agreed to participate in the trial, I didn’t know what the result would be,” Dana says. “But the side effects from the drug have not been bad, and I’m not in any pain from the tumor. It’s been amazing.”

The New England Journal of Medicine released the findings of an international, randomized phase 3 clinical trial of nirogacestat on March 9. The trial was directed by Dr. Gounder. Nirogacestat is a brand-new class of targeted medication known as a gamma-secretase inhibitor that inhibits a protein called Notch. According to the study, after taking nirogacestat, 41% of patients’ tumors were considerably reduced.

More than 75% of patients taking the targeted medication did not have tumor growth after two years, compared to only 44% of individuals taking a placebo. Fatigue (a sense of being exhausted), stomach issues, and skin rashes were the most frequent adverse effects. Dana has skin issues but is otherwise in good health.

Samuel Singer, MD, a famous sarcoma surgeon, was Dana’s first medical professional at MSK. After a second biopsy by Dr. Singer, MSK sarcoma pathologist Meera Hameed, MD, identified Dana’s soft tissue tumor as a desmoid tumor (also known as aggressive fibromatosis).

Desmoid tumors don’t metastasize to other regions of the body, in contrast to the majority of soft tissue sarcomas. Yet, these tumors have the potential to become exceedingly enormous, resulting in deformity, incapacity, and excruciating agony. Rarely, do they infect important organs, which can lead to serious difficulties or even death.

Dana was informed by Dr. Singer that while he could operate to remove the tumor, there was a strong possibility that it would return.

He referred her to Dr. Gounder, who is one of the world’s leading experts on desmoid tumors. Dr. Gounder has led several clinical trials studying drugs that target the defective proteins that cause these tumors to grow.

“Sarcoma itself is a rare disease, and desmoid tumors are a rare type of sarcoma,” Dr. Gounder explains, adding that only about 900 people are diagnosed with them in the United States every year. “MSK doesn’t only treat the major cancers,” he says. “We have expertise across more than 400 different types.”

Dana was originally prescribed sorafenib by Dr. Gounder (Nexavar). He had previously directed research that discovered this medication works for many individuals with desmoid tumors. However, the medication significantly raised Dana’s blood pressure. Allergies were brought on by another medication.

She was unable to pick up her little girls because of the tumor in her lower belly, which was becoming bigger. Finally, Dr. Gounder advised Dana to take into account the nirogacestat clinical trial. She began taking the medication in November 2019—three pills, twice daily.

Desmoid tumors are treated by a multidisciplinary team at MSK. To choose the most effective, individualized course of treatment for each patient, Dr. Gounder collaborates with interventional radiologist Joseph Erinjeri, MD, Ph.D., sarcoma surgeon Aimee Crago, MD, Ph.D., who also conducts research on desmoid tumors in her lab. Medications like nirogacestat and sorafenib, surgery, an interventional technique, or a combination of these may be used as therapies.

Image-guided therapy is Dr. Erinjeri’s area of expertise. One of these is cryoablation, which uses a specific, cold needle to make ice crystals inside a tumor, ultimately killing it. Another kind of treatment involves injecting tiny beads that have been loaded with chemotherapeutic medications right into the arteries that supply the tumor.

“These treatments can be very effective in patients who don’t respond to medications and who are not candidates for surgery,” Dr. Erinjeri says. “We’ve found that in patients who have these procedures and who are considered low risk, the chances of the tumor coming back are low.”

Radiologist Robert Lefkowitz, MD, who specializes in imaging sarcomas, is another important member of the team. He reviewed all the scans of the patients in the recent trial. “There were some very good responses,” he notes. “Many of the tumors were measurably smaller, including Dana’s.”

Most people diagnosed with a desmoid tumor are in their teens, 20s, or 30s. These growths are more common in women than in men, although experts don’t know why. The trial was unique because it included surveys about patients’ quality of life during treatment. “When developing new sarcoma drugs, we want to determine whether they make patients feel better, in addition to shrinking their tumors,” Dr. Gounder says.

The Desmoid Tumor Research Foundation (DTRF), a non-profit patient advocacy organization and MSK first collaborated to develop the instruments to assess a patient’s quality of life.

Nirogacestat also caused transient ovarian dysfunction, which was typically reversible, in a large number of female patients. The trial also included follow-up studies to examine reproductive function as a result. Dr. Gounder continues, “This tumor affects many people who may wish to have children, therefore this is a crucial step in developing new therapies.

Dana had these issues, but she wasn’t worried about them because she didn’t want any more kids.

Nirogacestat’s past is fascinating. Although it was initially designed to treat Alzheimer’s, it ultimately proved ineffective. Further tests against various cancer kinds produced equally unimpressive findings.

The leaders of the patient advocacy group DTRF noticed evidence showing the drug might be effective in treating desmoid tumors just as the drug’s manufacturer was about to give up on it. To create clinical trials and enlist patients as participants, the team collaborated with the pharmaceutical business and the National Cancer Institute.

“Our partnership with DTRF is an important part of this success story,” Dr. Gounder says. Drs. Gounder, Crago, and Lefkowitz all serve on DTRF’s Medical and Scientific Advisory Boards.

In addition to desmoid tumors, nirogacestat is now being evaluated in clinical trials for other cancers, including multiple myeloma.

Dana, whose daughters are now 4 and 7, lives in Pelham, New York, and has been able to continue working for most of her therapy. She is a special education third-grade teacher in a Bronx public school. She had to travel to Manhattan for the first round of the trial, but she can now have scans and other tests done at MSK Westchester, which is nearer to her home and place of employment.

“That makes it much easier because I don’t have to take the whole day off,” Dana says. “Participating in a clinical trial is a huge commitment, but it was worth it for me.”

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