Gangadharaiah Bharath B, Tansir Ghazal, Rastogi Sameer, Kaur Simran, Garg Vikas, Dhamija Ekta, Barwad Adarsh, Gamanagatti Shivanand, Bhoriwal Sandeep, Khan Maroof A
Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Physiology, All India Institute of Medical Sciences, New Delhi 110029, India.
Ecancermedicalscience. 2025 May 27;19:1915. doi: 10.3332/ecancer.2025.1915. eCollection 2025.
The duration of treatment for desmoid-type fibromatosis (DTF) is undefined. This study aimed to evaluate the efficacy of discontinuing sorafenib in responding patients with extremity DTF. We hereby report the initial findings comprising outcomes of 20 evaluable patients enrolled in this study.
This prospective single-arm phase 2 Simon's 2-stage trial enrolled adults with radiologically non-progressive, pain-free (Edmonton Symptom Assessment Scale (ESAS) score <2) extremity DTF post at least 1 year of sorafenib. Sorafenib was discontinued and patients were monitored by clinical examination, magnetic resonance imaging, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Addenbrooke's Cognitive Examination. Disease progression was defined as ≥10% increase in size plus ESAS >5 or ≥20% increase in size. The primary endpoint was a 1-year progression-free survival rate (PFR) after discontinuation. An unplanned analysis of the primary objective among 20 evaluable patients is being presented in this study.
33 patients had a median age of 29.5 years (range: 23-38) and a female-to-male ratio of 1.2:1. Median duration of sorafenib therapy was 24 months (range: 14.5-33.5), and at a median follow-up of 15 months (range: 9-18), 20 patients were evaluable. Among the 20 evaluable patients, 1-year change in tumour size ranged from a 21% decrease to a 32% increase. Three patients restarted sorafenib because of pain with stable disease ( = 2) and radiological progression ( = 1). 6-month and 1-year PFR was 96.7% and 95%, respectively. Statistically significant quality of life (QoL) improvement was demonstrated in insomnia ( = 0.01), diarrhea ( = 0.02), physical ( < 0.001) and social ( = 0.04) functioning at 12 months while neurocognitive functions remained stable.
As per the early results, stopping sorafenib can be potentially considered in responding patients with stable extremity DTF after at least 1 year of treatment. With improvement in QoL and an acceptable rate of disease progression upon stopping sorafenib, this treatment discontinuation strategy could be an important consideration in DTF management. Further analysis of the entire study cohort is warranted to establish optimal treatment duration for extremity DTF.
韧带样型纤维瘤病（DTF）的治疗持续时间尚无定论。本研究旨在评估在有反应的肢体DTF患者中停用索拉非尼的疗效。我们在此报告了本研究中20例可评估患者的初步研究结果。
这项前瞻性单臂2期西蒙两阶段试验纳入了成年患者，这些患者的肢体DTF经影像学检查无进展、无痛（埃德蒙顿症状评估量表（ESAS）评分<2），且已接受至少1年的索拉非尼治疗。停用索拉非尼后，通过临床检查、磁共振成像、欧洲癌症研究与治疗组织生活质量问卷核心30版和剑桥认知检查表对患者进行监测。疾病进展定义为肿瘤大小增加≥10%且ESAS>5或肿瘤大小增加≥20%。主要终点是停药后1年的无进展生存率（PFR）。本研究对20例可评估患者的主要目标进行了一项非计划分析。
33例患者的中位年龄为29.5岁（范围：23 - 38岁），女性与男性比例为1.2:1。索拉非尼治疗的中位持续时间为24个月（范围：14.5 - 33.5个月），中位随访15个月（范围：9 - 18个月），20例患者可评估。在这20例可评估患者中，肿瘤大小的1年变化范围为缩小21%至增大32%。3例患者因疼痛且疾病稳定（2例）和影像学进展（1例）而重新开始使用索拉非尼。6个月和1年的PFR分别为96.7%和95%。在12个月时，失眠（P = 0.01）、腹泻（P = 0.02）、身体功能（P < 0.001）和社交功能（P = 0.04）方面的生活质量（QoL）有统计学意义的改善，而神经认知功能保持稳定。
根据早期结果，对于接受至少1年治疗后肢体DTF病情稳定且有反应的患者，可考虑停用索拉非尼。随着生活质量的改善以及停用索拉非尼后疾病进展率可接受，这种停药治疗策略可能是DTF管理中的一个重要考虑因素。有必要对整个研究队列进行进一步分析，以确定肢体DTF的最佳治疗持续时间。
