RARE DISEASE
Desmoid tumor
Desmoid tumor
Desmoid tumor
Synonyms: Aggressive fibromatosis, Desmoid type fibromatosis
Synonyms: Aggressive fibromatosis, Desmoid type fibromatosis
Synonyms: Aggressive fibromatosis, Desmoid type fibromatosis
Drug discovery
7
drugs
With orphan designations
Overview
Desmoid tumors, also known as aggressive fibromatosis, are rare, non-metastatic fibroblastic neoplasms characterized by unpredictable growth and local invasiveness into surrounding tissues. With an annual incidence of 2–5 cases per million, they primarily affect adults aged 20–40 and show a 2:1 female predominance. Management prioritizes preserving function and quality of life due to their chronic, often debilitating nature.
Therapies
Active surveillance: First-line approach for asymptomatic/stable tumors [1][6][18].
Surgery: Reserved for low-morbidity cases (e.g., abdominal wall tumors) [1][11].
Medical therapy: TKIs (sorafenib, pazopanib), methotrexate/vinblastine, and gamma secretase inhibitors (nirogacestat FDA-approved in 2023) [1][13][16].
Categories: rare neoplastic diseases
Research Papers
1,215 drug discovery papers about Desmoid tumor, with 1 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,215 drug discovery papers about Desmoid tumor, with 1 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-29 | Deni Study: Real-World Data on the Use of Nirogacestat in Patients With Desmoid Tumors in the French Sarcoma Group.
The DeFi trial revealed a significant improvement in progression-free survival (PFS) with nirogacestat in patients with desmoid tumors. The DeNi study reports outcomes of patients treated with nirogacestat through the French compassionate use program. DeNi is a retrospective, real-world study. Outcomes included objective response, pain improvement, 1-year PFS, and toxicity. Between February and June 2024, 55 patients with desmoid tumors were included (37 women). Data were updated until November 2025. The median age was 38.6 years (range: 18.0-66.7). The median number of previous therapies was 2, including local therapies. The median follow-up was 21.4 months [95% CI: 19.5; 25.6]. The estimated median duration of nirogacestat treatment was 16 months. Partial response and stable disease were observed in 33 (60%) and 17 patients (31%), respectively. The 1-year PFS rate was 76.2%, and 77.0% of patients remained without treatment change at 1 year, including patients with dose reductions. Of the 49 patients with baseline pain, 38 (78%) experienced pain improvement under nirogacestat; 35 (71%) reduced or discontinued analgesics. The most frequent side effects (all grades) were diarrhea (53%), fatigue (47%), and rash (29%). Thirteen patients (24%) required dose reduction: 11 for digestive adverse events (85%), 1 for mucositis, and 1 for fatigue with hypertension. The DeNi study confirms the clinical benefits of nirogacestat in patients with desmoid tumors, with improvements in pain and tumor shrinkage observed in 60% of patients and PFS consistent with that reported in the phase III DeFi trial.
2026-07-25 | Retrospective Case Series Highlighting the Real-World Experience of Nirogacestat Therapy in Young Adults With Desmoid Tumors.
With a peak incidence in young adulthood, desmoid tumors (DTs) often cause pain, loss of function, and diminished quality of life. On the basis of findings from the Phase III desmoid fibromatosis (DeFi) trial, the selective gamma secretase inhibitor nirogacestat was approved by the US Food and Drug Administration (FDA) in November 2023 for the treatment of patients with DT. A retrospective, single-institution chart review of patients with DT who initiated nirogacestat therapy over a 14-month period was undertaken. Measured real-world outcomes included radiographic tumor response, patient-reported pain, and toxicities attributable to nirogacestat. Eleven young adult (YA) patients with DT who received nirogacestat were identified for the study. The median patient age was 26 years. The median duration of therapy at the time of the study was 8 months. RECIST responses included one patient with a partial response (PR), eight with stable disease (SD), and two were deemed radiologically inevaluable. Eight out of nine evaluable patients (88%) demonstrated a reduction in tumor volume and improvement in magnetic resonance imaging (MRI) T2-weighted signal intensity. Nine out of 10 patients who presented with pain (90%) reported rapid improvement. The most common toxicities included diarrhea, nausea, rash, and ovarian dysfunction. Discontinuation of nirogacestat was necessary in one patient due to severe diarrhea. Out of nine female patients, two elected to undergo oocyte cryopreservation prior to starting therapy. Nirogacestat provided therapeutic benefit in the majority of the YA DT population with rapid and sustained pain relief. The toxicity profile was generally predictable and manageable. The experience expands upon the findings of the DeFi Trial, defining the real-world benefits, toxicities, and supportive care needs.
2026-07-12 | Expert opinion document on the management of desmoid tumours in adult patients in Spain.
Desmoid tumours (DT), or aggressive fibromatosis are rare, nonmetastatic soft tissue neoplasms characterized by monoclonal fibroblast proliferation and infiltrative local behaviour that can affect organs and adjacent structures, resulting in sustained clinical burden and impacting patient's quality of life. The aim of this work is to determine the current management of DT in Spain, including unmet needs and to propose the positioning of nirogacestat in the current treatment algorithm. A literature review was conducted in June 2025 to identify published evidence on the epidemiology, diagnosis, management and unmet needs of DT in Spain. An expert panel of five Spanish oncologists specialized in sarcomas was convened. Each expert completed a questionnaire relating to research topics. Responses were consolidated and analysed, with a consensus threshold set at 80%. Findings were discussed and consensus reached at two virtual meetings. The therapeutic approach to DT is currently based on an individualized strategy according to symptoms and tumour's biological behaviour. In asymptomatic patients, active surveillance represents the first recommended strategy, given the potential for spontaneous tumour stabilization or regression. Symptomatic, functionally limiting, or documented progression cases require active treatment. The current unmet needs include lack of systemic treatments with approved indication and favourable safety profile. Nirogacestat, the first treatment authorised for patients with progressing DT who require systemic therapy, should be positioned as standard of care in the treatment algorithm. This first Spanish expert opinion document on DT management addresses evidence gaps and proposes a treatment algorithm to harmonise clinical practice.
2026-06-30 | Pelvic desmoid fibromatosis: a diagnostic and therapeutic challenge.
Pelvic desmoid fibromatosis is a rare locally aggressive benign neoplasm, typically presenting in the reproductive age group with lower abdominal pain. Extra-abdominal occurrence being predominant, the pelvic origin of the tumour makes the clinical management a multidisciplinary challenge. Previous surgeries, current or previous pregnancies, and familial adenomatous polyposis have been documented as associated risk factors. Our patient was a young woman with three previous caesarean sections, admitted with a large infiltrative lesion extending into the left pelvic sidewall up to the pelvic bone, causing ipsilateral severe hydroureteronephrosis. Malignancy was suspected due to the infiltrating nature of the lesion on imaging. Due to its proximity to the pelvic veins, preoperative embolisation of the feeding vessel was done. An exploratory laparotomy was performed by a multidisciplinary team. For this deep-seated disease, mass excision was performed along with total hysterectomy, left salpingo-oophorectomy and left ureteroneocystostomy. A part of the lesion infiltrating the presacral fascia was not removed during the primary surgery. Within 24 hours of surgery, she developed critical limb ischaemia in the left limb due to thrombosis in the ipsilateral external iliac artery. An emergency thrombo-embolectomy was performed by the vascular surgeons and thromboprophylaxis continued. Final histopathology confirmed desmoid fibromatosis. For the residual disease, the patient has been under close follow-up and is receiving targeted therapy with oral sorafenib to prevent local progression. Her follow-up imaging showed a decrease in the size of the residual disease and she is asymptomatic currently.
2026-06-28 | An unresectable desmoid tumour demonstrating long-term complete response to imatinib monotherapy: a case report.
Desmoid tumours are rare locally invasive soft tissue neoplasms arising from mesenchymal tissue that lack metastatic potential but have a high propensity for local recurrence. For unresectable mesenteric desmoid tumours requiring systemic therapy, the therapeutic landscape spans anti-hormonal combinations, chemotherapy, tyrosine kinase inhibitors, and gamma-secretase inhibitors. Imatinib is a multi-target tyrosine kinase inhibitor targeting PDGFR-alpha/beta and c-KIT that has demonstrated clinical activity in desmoid tumours with a favourable toxicity profile. We present a case of a 27-year-old white Australian man who presented with a large abdominal mass and weight loss. Imaging revealed a 23 × 12 × 21 cm mass that was diagnosed as a desmoid tumour via biopsy. The tumour was deemed to be unresectable and radiotherapy was considered to carry an unacceptable risk of toxicity. Initial treatment with tamoxifen and sulindac was unable to halt disease progression. The patient was subsequently commenced on imatinib 400 mg daily. Imaging after four months showed partial response, and over six years, complete radiological remission was achieved despite intermittent medication compliance. Aside from one episode of grade 1 photosensitivity, no significant toxicities were observed. Imatinib was self-ceased after ten years of treatment, and the patient remains disease-free at eleven years post-diagnosis under active surveillance. We describe a case of complete and durable remission achieved with imatinib monotherapy in an unresectable mesenteric desmoid tumour with the patient remaining disease-free at 10 years. This case highlights the potential for long-term complete response and underscores the need for prospective data to guide treatment duration and cessation criteria.
2026-07-29 | Deni Study: Real-World Data on the Use of Nirogacestat in Patients With Desmoid Tumors in the French Sarcoma Group.
The DeFi trial revealed a significant improvement in progression-free survival (PFS) with nirogacestat in patients with desmoid tumors. The DeNi study reports outcomes of patients treated with nirogacestat through the French compassionate use program. DeNi is a retrospective, real-world study. Outcomes included objective response, pain improvement, 1-year PFS, and toxicity. Between February and June 2024, 55 patients with desmoid tumors were included (37 women). Data were updated until November 2025. The median age was 38.6 years (range: 18.0-66.7). The median number of previous therapies was 2, including local therapies. The median follow-up was 21.4 months [95% CI: 19.5; 25.6]. The estimated median duration of nirogacestat treatment was 16 months. Partial response and stable disease were observed in 33 (60%) and 17 patients (31%), respectively. The 1-year PFS rate was 76.2%, and 77.0% of patients remained without treatment change at 1 year, including patients with dose reductions. Of the 49 patients with baseline pain, 38 (78%) experienced pain improvement under nirogacestat; 35 (71%) reduced or discontinued analgesics. The most frequent side effects (all grades) were diarrhea (53%), fatigue (47%), and rash (29%). Thirteen patients (24%) required dose reduction: 11 for digestive adverse events (85%), 1 for mucositis, and 1 for fatigue with hypertension. The DeNi study confirms the clinical benefits of nirogacestat in patients with desmoid tumors, with improvements in pain and tumor shrinkage observed in 60% of patients and PFS consistent with that reported in the phase III DeFi trial.
2026-07-25 | Retrospective Case Series Highlighting the Real-World Experience of Nirogacestat Therapy in Young Adults With Desmoid Tumors.
With a peak incidence in young adulthood, desmoid tumors (DTs) often cause pain, loss of function, and diminished quality of life. On the basis of findings from the Phase III desmoid fibromatosis (DeFi) trial, the selective gamma secretase inhibitor nirogacestat was approved by the US Food and Drug Administration (FDA) in November 2023 for the treatment of patients with DT. A retrospective, single-institution chart review of patients with DT who initiated nirogacestat therapy over a 14-month period was undertaken. Measured real-world outcomes included radiographic tumor response, patient-reported pain, and toxicities attributable to nirogacestat. Eleven young adult (YA) patients with DT who received nirogacestat were identified for the study. The median patient age was 26 years. The median duration of therapy at the time of the study was 8 months. RECIST responses included one patient with a partial response (PR), eight with stable disease (SD), and two were deemed radiologically inevaluable. Eight out of nine evaluable patients (88%) demonstrated a reduction in tumor volume and improvement in magnetic resonance imaging (MRI) T2-weighted signal intensity. Nine out of 10 patients who presented with pain (90%) reported rapid improvement. The most common toxicities included diarrhea, nausea, rash, and ovarian dysfunction. Discontinuation of nirogacestat was necessary in one patient due to severe diarrhea. Out of nine female patients, two elected to undergo oocyte cryopreservation prior to starting therapy. Nirogacestat provided therapeutic benefit in the majority of the YA DT population with rapid and sustained pain relief. The toxicity profile was generally predictable and manageable. The experience expands upon the findings of the DeFi Trial, defining the real-world benefits, toxicities, and supportive care needs.
2026-07-12 | Expert opinion document on the management of desmoid tumours in adult patients in Spain.
Desmoid tumours (DT), or aggressive fibromatosis are rare, nonmetastatic soft tissue neoplasms characterized by monoclonal fibroblast proliferation and infiltrative local behaviour that can affect organs and adjacent structures, resulting in sustained clinical burden and impacting patient's quality of life. The aim of this work is to determine the current management of DT in Spain, including unmet needs and to propose the positioning of nirogacestat in the current treatment algorithm. A literature review was conducted in June 2025 to identify published evidence on the epidemiology, diagnosis, management and unmet needs of DT in Spain. An expert panel of five Spanish oncologists specialized in sarcomas was convened. Each expert completed a questionnaire relating to research topics. Responses were consolidated and analysed, with a consensus threshold set at 80%. Findings were discussed and consensus reached at two virtual meetings. The therapeutic approach to DT is currently based on an individualized strategy according to symptoms and tumour's biological behaviour. In asymptomatic patients, active surveillance represents the first recommended strategy, given the potential for spontaneous tumour stabilization or regression. Symptomatic, functionally limiting, or documented progression cases require active treatment. The current unmet needs include lack of systemic treatments with approved indication and favourable safety profile. Nirogacestat, the first treatment authorised for patients with progressing DT who require systemic therapy, should be positioned as standard of care in the treatment algorithm. This first Spanish expert opinion document on DT management addresses evidence gaps and proposes a treatment algorithm to harmonise clinical practice.
2026-06-30 | Pelvic desmoid fibromatosis: a diagnostic and therapeutic challenge.
Pelvic desmoid fibromatosis is a rare locally aggressive benign neoplasm, typically presenting in the reproductive age group with lower abdominal pain. Extra-abdominal occurrence being predominant, the pelvic origin of the tumour makes the clinical management a multidisciplinary challenge. Previous surgeries, current or previous pregnancies, and familial adenomatous polyposis have been documented as associated risk factors. Our patient was a young woman with three previous caesarean sections, admitted with a large infiltrative lesion extending into the left pelvic sidewall up to the pelvic bone, causing ipsilateral severe hydroureteronephrosis. Malignancy was suspected due to the infiltrating nature of the lesion on imaging. Due to its proximity to the pelvic veins, preoperative embolisation of the feeding vessel was done. An exploratory laparotomy was performed by a multidisciplinary team. For this deep-seated disease, mass excision was performed along with total hysterectomy, left salpingo-oophorectomy and left ureteroneocystostomy. A part of the lesion infiltrating the presacral fascia was not removed during the primary surgery. Within 24 hours of surgery, she developed critical limb ischaemia in the left limb due to thrombosis in the ipsilateral external iliac artery. An emergency thrombo-embolectomy was performed by the vascular surgeons and thromboprophylaxis continued. Final histopathology confirmed desmoid fibromatosis. For the residual disease, the patient has been under close follow-up and is receiving targeted therapy with oral sorafenib to prevent local progression. Her follow-up imaging showed a decrease in the size of the residual disease and she is asymptomatic currently.
2026-06-28 | An unresectable desmoid tumour demonstrating long-term complete response to imatinib monotherapy: a case report.
Desmoid tumours are rare locally invasive soft tissue neoplasms arising from mesenchymal tissue that lack metastatic potential but have a high propensity for local recurrence. For unresectable mesenteric desmoid tumours requiring systemic therapy, the therapeutic landscape spans anti-hormonal combinations, chemotherapy, tyrosine kinase inhibitors, and gamma-secretase inhibitors. Imatinib is a multi-target tyrosine kinase inhibitor targeting PDGFR-alpha/beta and c-KIT that has demonstrated clinical activity in desmoid tumours with a favourable toxicity profile. We present a case of a 27-year-old white Australian man who presented with a large abdominal mass and weight loss. Imaging revealed a 23 × 12 × 21 cm mass that was diagnosed as a desmoid tumour via biopsy. The tumour was deemed to be unresectable and radiotherapy was considered to carry an unacceptable risk of toxicity. Initial treatment with tamoxifen and sulindac was unable to halt disease progression. The patient was subsequently commenced on imatinib 400 mg daily. Imaging after four months showed partial response, and over six years, complete radiological remission was achieved despite intermittent medication compliance. Aside from one episode of grade 1 photosensitivity, no significant toxicities were observed. Imatinib was self-ceased after ten years of treatment, and the patient remains disease-free at eleven years post-diagnosis under active surveillance. We describe a case of complete and durable remission achieved with imatinib monotherapy in an unresectable mesenteric desmoid tumour with the patient remaining disease-free at 10 years. This case highlights the potential for long-term complete response and underscores the need for prospective data to guide treatment duration and cessation criteria.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
7 orphan drug designations for Desmoid tumor, including 1 approved therapy.
7 orphan drug designations for Desmoid tumor, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
bi-functional antibody fusion protein targeting both cluster of differentiation 39 (CD39) and transforming growth factor beta (TGF-beta) | antibodies | FDA | 2026-02-15 | — | Elpiscience (Suzhou) Biopharma, Ltd. |
2,2'-((1''S,2R,2'S,5'S,8'S,10''E,12'Z,18''S,21''S,27''S,30''S,33''S,42''S,45''S,48''S)-1-acetyl-42''-(((S)-1-amino-1-oxopropan-2-yl)carbamoyl)-45''-(benzo[b]thiophen-3-ylmethyl)-30''-benzyl-21''-(3-carboxybenzyl)-24'',24'',27''-trimethyl-5'-neopentyl-3',5'',6',16',16'',19'',22'',25'',28'',31'',39'',44'',47'',50'',52''-pentadecaoxo-48''-(thiophen-3-ylmethyl)-6''-oxa-1',4',4'',7',17'',20'',23'',26'',29'',32'',38'',43'',46'',49'',51''-pentadecaazadispiro[pyrrolidine-2,15'-cyclohexadecane-8',15''-tricyclo[31.17.2.11,4]tripentacontane]-10'',12'-dien-2',18''-diyl)diacetic acid | small molecules | FDA | 2026-01-29 | — | Parabilis Medicines, Inc. |
varegacestat | small molecules | FDA | 2023-11-02 | — | Immunome, Inc. |
sorafenib | small molecules | FDA | 2019-02-28 | — | Bayer HealthCare Pharmaceuticals, Inc. |
nirogacestat [Ogsiveo] | small molecules | FDA | 2018-06-07 | 2023-11-27 | SpringWorks Therapeutics, Inc. |
tegavivint | small molecules | FDA | 2018-04-11 | — | Beta Cat Pharmaceuticals |
Toremifene | small molecules | FDA | 1993-08-17 | — | Orion Corporation |
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