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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
PMID: 30575484    PMCID: PMC6447029    URL: https://www.ncbi.nlm.nih.gov/pubmed/30575484
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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. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT02066181 .).
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1533-4406 Gounder, Mrinal M Mahoney, Michelle R Van Tine, Brian A Ravi, Vinod Attia, Steven Deshpande, Hari A Gupta, Abha A Milhem, Mohammed M Conry, Robert M Movva, Sujana Pishvaian, Michael J Riedel, Richard F Sabagh, Tarek Tap, William D Horvat, Natally Basch, Ethan Schwartz, Lawrence H Maki, Robert G Agaram, Narasimhan P Lefkowitz, Robert A Mazaheri, Yousef Yamashita, Rikiya Wright, John J Dueck, Amylou C Schwartz, Gary K Journal Article United States U10 CA180858/CA/NCI NIH HHS/ UG1 CA189850/CA/NCI NIH HHS/ R01 FD005105/FD/FDA HHS/ U10 CA180821/CA/NCI NIH HHS/ U10 CA180838/CA/NCI NIH HHS/ P30 CA008748/CA/NCI NIH HHS/ U10 CA180857/CA/NCI NIH HHS/ U10 CA180833/CA/NCI NIH HHS/ U10 CA180882/CA/NCI NIH HHS/ U24 CA196171/CA/NCI NIH HHS/ U10 CA180826/CA/NCI NIH HHS/ U10 CA180888/CA/NCI NIH HHS/ U10 CA180820/CA/NCI NIH HHS/ U10 CA180868/CA/NCI NIH HHS/ UG1 CA189957/CA/NCI NIH HHS/ Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural N Engl J Med. 2018 Dec 20;379(25):2417-2428. doi: 10.1056/NEJMoa1805052.