Journal article
Sorafenib for Advanced and Refractory Desmoid Tumors
The New England journal of medicine, Vol.379(25), pp.2417-2428
12/20/2018
DOI: 10.1056/NEJMoa1805052
PMCID: PMC6447029
PMID: 30575484
Abstract
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.
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.
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%).
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 .).
Details
- Title: Subtitle
- Sorafenib for Advanced and Refractory Desmoid Tumors
- Creators
- Mrinal M Gounder - Cornell UniversityMichelle R Mahoney - Mayo ClinicBrian A Van Tine - Washington University in St. LouisVinod Ravi - The University of Texas MD Anderson Cancer CenterSteven Attia - Mayo Clinic in FloridaHari A Deshpande - Yale UniversityAbha A Gupta - Princess Margaret Cancer CentreMohammed M Milhem - University of IowaRobert M Conry - University of Alabama at BirminghamSujana Movva - Fox Chase Cancer CenterMichael J Pishvaian - Georgetown UniversityRichard F Riedel - Duke UniversityTarek Sabagh - Institute Community Oncology Research ProgramWilliam D Tap - Cornell UniversityNatally Horvat - Cornell UniversityEthan Basch - University of North Carolina at Chapel HillLawrence H Schwartz - Columbia UniversityRobert G Maki - Cold Spring Harbor LaboratoryNarasimhan P Agaram - Cornell UniversityRobert A Lefkowitz - Cornell UniversityYousef Mazaheri - Cornell UniversityRikiya Yamashita - Cornell UniversityJohn J Wright - National Institutes of HealthAmylou C Dueck - Mayo Clinic, Scottsdale AZ.Gary K Schwartz - Columbia University
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.379(25), pp.2417-2428
- DOI
- 10.1056/NEJMoa1805052
- PMID
- 30575484
- PMCID
- PMC6447029
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Grant note
- U10 CA180868 / NCI NIH HHS U10 CA180821 / NCI NIH HHS U10 CA180857 / NCI NIH HHS P50 CA217694 / NCI NIH HHS U10 CA180882 / NCI NIH HHS R01 FD005105 / FDA HHS U24 CA196171 / NCI NIH HHS U10 CA180833 / NCI NIH HHS P30 CA008748 / NCI NIH HHS U10 CA180863 / NCI NIH HHS P30 CA086862 / NCI NIH HHS U10 CA180820 / NCI NIH HHS U10 CA180858 / NCI NIH HHS U10 CA180826 / NCI NIH HHS UG1 CA233329 / NCI NIH HHS UG1 CA189850 / NCI NIH HHS UG1 CA189957 / NCI NIH HHS U10 CA180838 / NCI NIH HHS U10 CA180888 / NCI NIH HHS
- Language
- English
- Date published
- 12/20/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359920002771
Metrics
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