In a phase III trial reported in The New England Journal of Medicine, Gounder et al found that sorafenib improved progression-free survival vs placebo in patients with progressive, symptomatic, or recurrent desmoid tumors. As noted by the investigators, there is no current standard of care for these connective tissue neoplasms, which may infiltrate the mesentery, neurovascular structures, and visceral organs.
In the double-blind trial, 87 patients from 24 U.S. sites were randomly assigned 1.7:1 between March 2014 and January 2016 to receive sorafenib 400 mg once daily (n = 50) or placebo (n = 37). Crossover to sorafenib was permitted for patients in the placebo group who had disease progression.
The primary endpoint was investigator-assessed progression-free survival.
Median follow-up was 27.2 months. Progression-free survival was 89% in the sorafenib group vs 46% in the placebo group at 1 year and 81% vs 36% at 2 years (hazard ratio [HR] = 0.13, P < .001). Prior to crossover from the placebo to sorafenib group, objective response rates were 33% in the sorafenib group and 20% in the placebo group. Median time to objective response was 9.6 months vs 13.3 months. Objective responses were ongoing at time of analysis.
The most common adverse events in the sorafenib group were grade 1 or 2 rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). Grade 3 or 4 adverse events occurred in 47% of patients treated with sorafenib vs 25% of those treated with placebo, with the most common in the sorafenib group being any rash or skin disorder (14%). Treatment-related grade 3 adverse events occurred in 29% of the sorafenib group vs 14% of the placebo group. Treatment-related grade 4 events in the sorafenib group included thrombocytopenia (2%) and anemia (2%). Adverse events led to treatment discontinuation in 20% vs 0% of patients.
The investigators concluded, “Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses.”
Disclosure: The study was funded by the National Cancer Institute and others. The study authors’ full disclosures can be found at nejm.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.