Sorafenib treatment duration in desmoid tumors.
Authors: Costa Philippos Apolinario , Yi Irvin , Arora Arshia , Hardy Nicole Janell , Bialick Steven , Espejo-Freire Andrea P. , Jonczak Emily E , Olino Kelly , D'Amato Gina Z. , Trent Jonathan C. , Deshpande Hari Anant 
Published: June 2024

11585

Background: Desmoid tumors are soft-tissue neoplasms, which, although unable to metastasize, can cause significant morbidity due to local invasion. Currently, the first-line approach is active surveillance. For tumors that progress during surveillance, systemic therapies can be used, including nirogacestat, sorafenib, pazopanib, and cytotoxic chemotherapy. However, their optimal duration is unknown. Here, we aim to assess the risk of treatment failure after discontinuing sorafenib before one year. Methods: We analyzed all patients with desmoid tumors treated with sorafenib at three academic centers from 01/01/2000-12/01/2021. We included patients who discontinued sorafenib not due to radiological or clinical progression and had documented no intention to start the next line of therapy at the time of discontinuation. The primary endpoint was 2-year treatment-free survival between patients who stopped sorafenib before and after 1 year. The secondary endpoint was the rate of toxic effects recorded according to the Common Terminology Criteria for Adverse Events during treatment. We calculated treatment-free survival using the Kaplan-Meier method with the Log-Rank Test to estimate the 95% confidence interval. All patients were censored at the 2-year mark. Fischer’s Exact T-test was performed to assess between-group differences. Results: 40 patients received sorafenib and discontinued it with no intention to start a next line of therapy. The main reasons for discontinuation were side effects (n=21, 52%) and physician-patient preference (n=10, 25%). 27 (67%)were women, and median age at diagnosis was 36.Regarding race and ethnicity,27 (47%)were White, 8 (20%)were Black, and 16 (40%) were Latino. The tumor was in the lower extremity in 10 (25%) cases, trunk in 3 (7%) cases, abdominal wall in 10 (25%), intra-abdominal in 5 (12%), upper extremity in 5 (12%) head-neck in 1 and breast in 1. 20 patients stopped treatment before one year and 20 after one year, with 7 and 3 patients requiring a next line of therapy in each group, respectively. The 2-year treatment-free survival was 60% (95% confidence interval [CI], 0.35 to 0.85) in the prior to 1-year group and 87.5% (95% CI, 0.71 to 1.0) in the post-1-year group (P = 0.046). The most frequently reported adverse events while on sorafenib were grade 1 or 2 events of palmar-plantar erythrodysesthesia (40%) and diarrhea (40%), with no difference between groups on therapy discontinuation due to side effects (p=0.1). Conclusions: Discontinuing sorafenib prior to 1 year was associated with a higher risk of requiring further therapy within the following two years. Still, most patients did not require additional therapy. This finding underscores the complexity of determining the optimal duration for sorafenib therapy, and multiple features should be considered, including side effects, symptom improvement, fertility planning, tumor cellularity (evaluated by T2 MRI signal), and physician-patient shared decision.