Sorafenib for advanced and refractory desmoid tumors Journal Article


Authors: Gounder, M. M.; Mahoney, M. R.; Van Tine, B. A.; Ravi, V.; Attia, S.; Deshpande, H. A.; Gupta, A. A.; Milhem, M. M.; Conry, R. M.; Movva, S.; Pishvaian, M. J.; Riedel, R. F.; Sabagh, T.; Tap, W. D.; Horvat, N.; Basch, E.; Schwartz, L. H.; Maki, R. G.; Agaram, N. P.; Lefkowitz, R. A.; Mazaheri, Y.; Yamashita, R.; Wright, J. J.; Dueck, A. C.; Schwartz, G. K.
Article Title: Sorafenib for advanced and refractory desmoid tumors
Abstract: BACKGROUND Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care. METHODS In this double-blind, phase 3 trial, we randomly assigned 87 patients with progressive, symptomatic, or recurrent desmoid tumors to receive either sorafenib (400- mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated. RESULTS With a median follow-up of 27.2 months, the 2-year progression-free survival rate was 81% (95% confidence interval [CI], 69 to 96) in the sorafenib group and 36% (95% CI, 22 to 57) in the placebo group (hazard ratio for progression or death, 0.13; 95% CI, 0.05 to 0.31; P<0.001). Before crossover, the objective response rate was 33% (95% CI, 20 to 48) in the sorafenib group and 20% (95% CI, 8 to 38) in the placebo group. The median time to an objective response among patients who had a response was 9.6 months (interquartile range, 6.6 to 16.7) in the sorafenib group and 13.3 months (interquartile range, 11.2 to 31.1) in the placebo group. The objective responses are ongoing. Among patients who received sorafenib, the most frequently reported adverse events were grade 1 or 2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). CONCLUSIONS Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses. © 2018 Massachusetts Medical Society.
Journal Title: New England Journal of Medicine
Volume: 379
Issue: 25
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2018-12-20
Start Page: 2417
End Page: 2428
Language: English
DOI: 10.1056/NEJMoa1805052
PROVIDER: scopus
PUBMED: 30575484
PMCID: PMC6447029
DOI/URL:
Notes: New Engl. J. Med. -- Export Date: 2 January 2019 -- Article -- CODEN: NEJMA C2 - 30575484 -- Source: Scopus
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  1. Narasimhan P Agaram
    190 Agaram
  2. Mrinal M Gounder
    229 Gounder
  3. William Douglas Tap
    375 Tap
  4. Natally Horvat
    101 Horvat