Chapter 7 166 Safety and efficacy of gamma-secretase inhibitor nirogacestat (PF03084014) in desmoid tumor: Report of four pediatric/young adult cases Setup This case series describes treatment with nirogacestat (PF-03084014) in desmoid tumor in four cases via compassionate use. Data were retrospectively collected. The drug was provided by SpringWorks Therapeutics. Comments on ethical approval, funding or informed consent are lacking in the manuscript. Patients Four pediatric patients, aged of 2.5, 4, 17, and 19 years old, were included in the expanded access program to treat desmoid tumors, a type of typically non-cancerous soft tissue tumor. Of these patients, three had previously undergone surgery and/or systemic therapy, while the fourth patient received nirogacestat as initial treatment. The choice of nirogacestat was based on its anticipated low toxicity profile, severe pain at the tumor sites due to prior treatment failure, and in the case of the 2.5-year-old patient, due to the unavailability of alternative systemic therapy options following progression of the tumor after eight lines of therapy. Interventions Patients received nirogacestat (PF-03084014), a selective gamma-secretase inhibitor at 90 mg/ m2 twice a day. Treatment duration ranged from six to 18 months. One patient simultaneously received celecoxib. Outcome Tumor response, response duration and adverse events were reported. One patient continued to have complete remission for nine months at time of publication. Two patients achieved stable disease, with a tumor size reduction of 18% and 42% for 17 and nine months, respectively, and the fourth patient progressed after a partial response. Only one grade 2 adverse event (diarrhea) was reported. Comparison with other data The authors were unable to compare the observed efficacy and safety with other data on nirogacestat, since no other data from pediatric and young adult patients were available. Importantly, the authors were the first to administer the drug dissolved in water, which was necessary for administration to the youngest patient. However, the authors ‘have not conducted bioavailability or pharmacokinetic studies of nirogacestat administered in this manner’. The authors therefore note that: ‘it remains unknown whether dissolution in water adversely impacts
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