Pazopanib therapy for adolescent and young adult desmoid tumors.

10547 Background: There is a lack of reliably effective medical therapies for desmoid tumors (DT). Surgical resection may be morbid, and even a complete resection does not preclude recurrence. Radiotherapy is associated with potentially severe late-effects, a risk that may be particularly detrimental in young patients. In a previous review of our single institution DT experience, we found that objective treatment responses to medical therapies were rare.However,we have recently observed promising effect from therapy with the tyrosine kinase inhibitor pazopanib in adolescent and young adult (AYA) patients with DT. Methods: Retrospective single institution chart review evaluating all pazopanib treatment in AYA patients with DT. Results: Five AYA patients, ages 15-21 years, with previously treated DT received pazopanib. Four patients with sporadic DT were documented by next generation sequencing to have mutations of CTNNB1, and 1 patient with intra-abdominal tumors following colectomy was known to carry a large germline interstitial chromosomal deletion (5q21.2q23.1) including the APC locus. The median duration of pazopanib treatment was 6 months at the time of analysis (range: 5-21), with treatment ongoing for 4 patients. None of the patients demonstrated progressive disease while on treatment. Best responses by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) were partial response in 3 of 5 and stable disease in 2 of 5 cases. One response was nearly complete. In one case of stable disease, tumor necrosis was evident on magnetic resonance imaging after 2 months on pazopanib. Four patients reported pain relief while on pazopanib, including one patient with stable disease. Pazopanib was discontinued in 1 patient after 18 months due to recurrent facial edema. Other grade 1-2 adverse effects responded to dose reduction. The only grade 3 adverse effect was increasing weakness in a patient with pre-existing myopathy; this patient tolerated pazopanib at a reduced dose. Conclusions: This is the first report of objective responses to pazopanib by RECIST criteria in AYA patients with DT. Given these benefits and relatively mild toxicity, we conclude that pazopanib therapy should be considered in this patient population.