Inhibiting the proliferation of desmoid tumors with Nirogacestat
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Reviewed by Dat Tien Nguyen, B.A, ScM.
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Posted on March 17th, 2023
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Despite being non-metastatic, desmoid tumors can cause severe pain and affect function if the tumor compresses the organs. These cells produced an abnormally high amount of the Notch-1 protein which can further worsen the patient’s prognosis. Nirogacestat is an γ-secretase inhibitor that can interfere with Notch signaling. Thus, the SpringWork Therapeutics pharmaceutical company had funded a study to investigate the possibility of using Nirogacestat to treat desmoid tumors.
The phase 3 clinical trial included 142 patients who were diagnosed with desmoid tumors using histology. The average age of these patients was 34 years old; 75% of them have tumors located outside of the abdominal cavity, and the average tumor size is between 92 and 115 mm. As Nirogacestat helped prevent tumor progression and death in 76% of the patients after 2 years. This outcome happened in 44% of those in the placebo group. Thus, the researchers concluded that, after 2 years of treatment, Nirogacestat reduced the risk of mortality and tumor enlargement by 71% when compared to the placebo group. In addition, tumor size was also quantified with MRI imaging, and the study found that partial shrinkage of the tumor was detected in 41% of the patients treated with Nitrogacestat; whereas, partial shrinkage was only observed in 8% of the placebo groups. Furthermore, 7% of those treated with Nitrogacestat reported complete shrinkage of the tumor; this was not observed in the placebo group. In addition, Nitrogacestat took less time to produce positive outcomes. 50% of cases of tumor shrinkage were reported after 5.6 months of treatment; median time to response took around 11 months for those in the placebo group. As a result of the effect on tumor size, Nirogacestat also relieved pain, helped patients regain their daily life function, and improved their quality of life. Albeit, Nirogacestat was associated with some mild adverse effects, commonly reported by 30% to 50% of the patients, in the form of nausea, fatigue, hypophosphatemia, and maculopapular rash. However, it is important to note that 75% of pregnant women who were treated with Nirogacestat experienced ovarian dysfunction which was relieved upon dose reduction. Thus, it is important to further investigate the safety profile of Nirogacestat on expecting mothers and newborn.
The phase 3 clinical trial included 142 patients who were diagnosed with desmoid tumors using histology. The average age of these patients was 34 years old; 75% of them have tumors located outside of the abdominal cavity, and the average tumor size is between 92 and 115 mm. As Nirogacestat helped prevent tumor progression and death in 76% of the patients after 2 years. This outcome happened in 44% of those in the placebo group. Thus, the researchers concluded that, after 2 years of treatment, Nirogacestat reduced the risk of mortality and tumor enlargement by 71% when compared to the placebo group. In addition, tumor size was also quantified with MRI imaging, and the study found that partial shrinkage of the tumor was detected in 41% of the patients treated with Nitrogacestat; whereas, partial shrinkage was only observed in 8% of the placebo groups. Furthermore, 7% of those treated with Nitrogacestat reported complete shrinkage of the tumor; this was not observed in the placebo group. In addition, Nitrogacestat took less time to produce positive outcomes. 50% of cases of tumor shrinkage were reported after 5.6 months of treatment; median time to response took around 11 months for those in the placebo group. As a result of the effect on tumor size, Nirogacestat also relieved pain, helped patients regain their daily life function, and improved their quality of life. Albeit, Nirogacestat was associated with some mild adverse effects, commonly reported by 30% to 50% of the patients, in the form of nausea, fatigue, hypophosphatemia, and maculopapular rash. However, it is important to note that 75% of pregnant women who were treated with Nirogacestat experienced ovarian dysfunction which was relieved upon dose reduction. Thus, it is important to further investigate the safety profile of Nirogacestat on expecting mothers and newborn.