The Desmoid Tumor Research Foundation

June 2018

Phase III, randomized, double blind, placebo-controlled trial of sorafenib in desmoid tumors

Author Information

M Gounder, M Mahoney, B Van Tine, V Ravi, S Attia, H Deshpande, A Gupta, M Milhem, R Conry, S Movva, M Pishvaian, J Crawford, T Sabagh, R Maki, W Tap, R Lefkowitz, N Agaram, J Wright, A Dueck, G Schwartz

Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Mayo Clinic, Rochester, MN; Washington University in St. Louis, St. Louis, MO; Dept of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Mayo Clinic, Jacksonville, FL; Yale Cancer Center, New Haven, CT; Princess Margaret Cancer Centre, Toronto, ON, Canada; University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City, IA; The Kirkland Clinic At Acton Road, Birmingham, AL; Fox Chase Cancer Center, Philadelphia, PA; Georgetown University Medical Center, Washington, DC; Duke University Medical Center, Durham, NC; Hem and Onc of Dayton Inc, Dayton, OH; Monter Cancer Center, Northwell Health and Cold Spring Harbor Laboratory, Lake Success, NY; Dept of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan Kettering Cancer Center, New York, NY; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Mayo Clinic, Scottsdale, AZ; Columbia University Medical Center, New York, NY

Publication

J Clin Onc

Summary

We conducted an international prospective study to evaluate efficacy of Sorafanib (400 mg qd) in unresectable progressive (PD) or symptomatic desmoid tumors (DT). Pts were randomized 2:1 (S:P) and crossover to S upon RECIST 1.1 PD. Primary endpoint was progression-free survival (PFS). 75 pts yielded 90% power (1-sided = 0.025, 1 interim analysis) to detect a hazard ratio (HR) of 0.4 (favoring S), assuming 6 month (mo) median (md) PFS for P and 15 mo for S, requiring 52 PFS events. Other endpoints: response rates (RR); toxicity (tox); overall survival; patient-reported outcome (PRO); tumor and imaging biomarkers. Results: 87 pts (37 P, 50 S) enrolled over 17 mo at 25 sites [69% female, md age 37 years (yr) (range 18-72), 62% chemo-naive, 9% prior RT]. Tumor location and pain level were balanced. 30% (11/37) P and 38% (19/50) S pts continue; 18% (9/50) ended S due to tox (0% P). 33% (16/49) S, 14% (5/36) P pts had grade 3-4 tox, primarily rash, hypertension, fatigue, pain. For the 1st 75 evaluable pts (med f/u 26 mo): PD 69% (22/32) P, 16% (7/43) S, 1 death (S); Durable partial RR 33% (14/43, 2Ð28 mo) on S and 21% (7/32, 4Ð17 mo) on P (p = 0.3); 1-yr PFS: 43%-P, 87%-S; Med PFS: 9.4 mo (95% CI 5.7-NE) for P, not reached for S [HR = 0.14 (95% CI 0.06-0.33), p<0.0001)]. Analyses of PRO, MRI T2 signal and tumor biopsy are ongoing. Conclusions: Phase III studies in rare cancers are feasible and rapidly conducted in an NCTN group setting. Here, S was well tolerated with significantly improved PFS. Spontaneous RR on P is consistent with observational trials in DT. The study exceeded its primary endpoint for PFS. DSMB recommended unblinding (P offered S). S may represent a new 1st-line or subsequent-line SoC in select pts with DT.

View Abstract