Desmoid tumor

Section editor
	Elizabeth J. Davis, MD Vanderbilt University Nashville, TN, USA

Note: these are regimens tested in subtype-specific populations, please see the main soft tissue sarcoma page for other regimens. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

5 regimens on this page 7 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

French Intergroup

• 2022: Benech et al. Desmoid tumors located in the abdomen or associated with adenomatous polyposis: French intergroup clinical practice guidelines for diagnosis, treatment, and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR) PubMed

NCCN

• NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Soft Tissue Sarcoma.

All lines of therapy

Imatinib monotherapy

Regimen variant #1, fixed dose

Study	Dates of enrollment	Evidence
Kasper et al. 2017 (GISG-01)	2010-2013	Phase 2

Targeted therapy

• Imatinib (Gleevec) 800 mg PO once per day

2 years of therapy

Regimen variant #2, BSA-based dosing

Study	Dates of enrollment	Evidence
Chugh et al. 2010	2002-10 to 2005-12	Phase 2

Targeted therapy

• Imatinib (Gleevec) by the following BSA-based criteria:
  • 1.50 m² or more: 300 mg PO twice per day
  • 1.00 to 1.49 m²: 200 mg PO twice per day
  • Less than 1.00 m²: 100 mg PO twice per day

Continued indefinitely

References

1. Chugh R, Wathen JK, Patel SR, Maki RG, Meyers PA, Schuetze SM, Priebat DA, Thomas DG, Jacobson JA, Samuels BL, Benjamin RS, Baker LH; Sarcoma Alliance for Research through Collaboration (SARC). Efficacy of imatinib in aggressive fibromatosis: Results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial. Clin Cancer Res. 2010 Oct 1;16(19):4884-91. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed
2. GISG-01: Kasper B, Gruenwald V, Reichardt P, Bauer S, Rauch G, Limprecht R, Sommer M, Dimitrakopoulou-Strauss A, Pilz L, Haller F, Hohenberger P. Imatinib induces sustained progression arrest in RECIST progressive desmoid tumours: Final results of a phase II study of the German Interdisciplinary Sarcoma Group (GISG). Eur J Cancer. 2017 May;76:60-67. Epub 2017 Mar 8. link to original article contains dosing details in manuscript PubMed NCT01137916

Methotrexate & Vinblastine

Regimen

Study	Dates of enrollment	Evidence
Skapek et al. 2007 (POG 9650)	1997-2001	Phase 2
Toulmonde et al. 2019 (DESMOPAZ)	2012-2017	Randomized Phase 2

Note: DESMOPAZ was randomized but non-comparative.

Chemotherapy

• Methotrexate (MTX) 30 mg/m² IV once on day 1
• Vinblastine (Velban) 5 mg/m² IV once on day 1

7-day cycle for 26 cycles, then 14-day cycle for 13 cycles

References

1. POG 9650: Skapek SX, Ferguson WS, Granowetter L, Devidas M, Perez-Atayde AR, Dehner LP, Hoffer FA, Speights R, Gebhardt MC, Dahl GV, Grier HE; Pediatric Oncology Group. Vinblastine and methotrexate for desmoid fibromatosis in children: results of a Pediatric Oncology Group Phase II Trial. J Clin Oncol. 2007 Feb 10;25(5):501-6. link to original article contains dosing details in manuscript PubMed
2. DESMOPAZ: Toulmonde M, Pulido M, Ray-Coquard I, Andre T, Isambert N, Chevreau C, Penel N, Bompas E, Saada E, Bertucci F, Lebbe C, Le Cesne A, Soulie P, Piperno-Neumann S, Sweet S, Cecchi F, Hembrough T, Bellera C, Kind M, Crombe A, Lucchesi C, Le Loarer F, Blay JY, Italiano A. Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol. 2019 Sep;20(9):1263-1272. Epub 2019 Jul 19. link to original article contains dosing details in abstract PubMed NCT01876082

Nirogacestat monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gounder et al. 2023 (DeFi)	2019-05 to 2020-08	Phase 3 (E-RT-esc)	Placebo	Superior PFS (primary endpoint) PFS24: 76% vs 44% (HR 0.29, 95% CI 0.15-0.55)

Targeted therapy

• Nirogacestat (Ogsiveo) 150 mg PO twice per day

Continued indefinitely

References

1. DeFi: Gounder M, Ratan R, Alcindor T, Schöffski P, van der Graaf WT, Wilky BA, Riedel RF, Lim A, Smith LM, Moody S, Attia S, Chawla S, D'Amato G, Federman N, Merriam P, Van Tine BA, Vincenzi B, Benson C, Bui NQ, Chugh R, Tinoco G, Charlson J, Dileo P, Hartner L, Lapeire L, Mazzeo F, Palmerini E, Reichardt P, Stacchiotti S, Bailey HH, Burgess MA, Cote GM, Davis LE, Deshpande H, Gelderblom H, Grignani G, Loggers E, Philip T, Pressey JG, Kummar S, Kasper B. Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors. N Engl J Med. 2023 Mar 9;388(10):898-912. link to original article contains dosing details in abstract PubMed NCT03785964

Pazopanib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Toulmonde et al. 2019 (DESMOPAZ)	2012-2017	Randomized Phase 2

Note: this study was randomized but non-comparative.

Targeted therapy

• Pazopanib (Votrient) 800 mg PO once per day

Up to 12 months of therapy

References

1. DESMOPAZ: Toulmonde M, Pulido M, Ray-Coquard I, Andre T, Isambert N, Chevreau C, Penel N, Bompas E, Saada E, Bertucci F, Lebbe C, Le Cesne A, Soulie P, Piperno-Neumann S, Sweet S, Cecchi F, Hembrough T, Bellera C, Kind M, Crombe A, Lucchesi C, Le Loarer F, Blay JY, Italiano A. Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study. Lancet Oncol. 2019 Sep;20(9):1263-1272. Epub 2019 Jul 19. link to original article contains dosing details in abstract PubMed NCT01876082

Pegylated liposomal doxorubicin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Constantinidou et al. 2009	2006-2009	Case series

Chemotherapy

• Pegylated liposomal doxorubicin (Doxil) 50 mg/m² IV over 60 minutes once on day 1

28-day cycles

References

1. Case series: Constantinidou A, Jones RL, Scurr M, Al-Muderis O, Judson I. Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur J Cancer. 2009 Nov;45(17):2930-4. Epub 2009 Sep 18. link to original article PubMed

Sorafenib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gounder et al. 2018 (Alliance A091105)	2014-2016	Phase 3 (E-esc)	Placebo	Superior PFS PFS24: 81% vs 36% (HR 0.13, 95% CI 0.05-0.31)

Targeted therapy

• Sorafenib (Nexavar) 400 mg PO once per day on days 1 to 28

28-day cycles

References

1. Alliance A091105: Gounder MM, Mahoney MR, Van Tine BA, Ravi V, Attia S, Deshpande HA, Gupta AA, Milhem MM, Conry RM, Movva S, Pishvaian MJ, Riedel RF, Sabagh T, Tap WD, Horvat N, Basch E, Schwartz LH, Maki RG, Agaram NP, Lefkowitz RA, Mazaheri Y, Yamashita R, Wright JJ, Dueck AC, Schwartz GK. Sorafenib for Advanced and Refractory Desmoid Tumors. N Engl J Med. 2018 Dec 20;379(25):2417-2428. link to original article contains dosing details in abstract link to PMC article PubMed NCT02066181