What we know about the therapeutic landscape of desmoid tumors: an analysis of clinical trials registered on clinicaltrials.gov

Desmoid tumours are rare mesenchymal neoplasms that infiltrate deep soft tissues locally but do not metastasize. Due to the scarcity of the disease, defining the most appropriate treatment is challenging. Most experts acknowledge the use of active surveillance for asymptomatic patients. Surgical resection of the tumour has fallen out of favour because of the high risk of recurrence and co-morbidities. Therefore, over the last few decades, advances in systemic therapy have been mounting, including chemotherapy, hormonal therapy, and targeted agents. Recently, nirogacestat, a selective NOTCH signalling inhibitor, has been approved by the US FDA as the primary treatment for progressive desmoid tumours. We leveraged the ClinicalTrials.gov database to obtain detailed, up-to-date figures on registered clinical trials for desmoid tumours, focusing on completed trials with interventional therapeutic aims. Our study identified 62 trials related to desmoid tumours, covering various characteristics and clinical phases to date. The analysis of these trials revealed that the number of completed interventional clinical trials has increased over the past years, aimed at investigating the safety and efficacy of various modalities. These completed trials publish results at a significantly higher rate (23.1%) than ongoing trials (3.8%), p=0.043. Also, advanced-phase trials lead in transparency (50% reporting), and drug interventions outperform other types (16.2%). Nonetheless, collective analysis unveiled that only 11.3% of all trial types have posted their results; thus, a critical knowledge gap remains, warranting further data exploration. Finally, we comprehensively discussed the completed interventional trials conducted from inception to 2025. These studies assessed the clinical benefits and toxicity of various systemic therapies for desmoid tumours. While our analysis provides a consolidated reference tool for multiple therapeutic modalities for DT, further data exploration beyond the ClinicalTrials.gov platform is needed to produce a more comprehensive and validated figure. Moreover, additional preclinical investigations are needed to further explore the molecular biology of desmoid tumours, thereby providing a clearer picture of potential druggable targets.