Results From Phase 3 Trial Report Sorafenib Show Positive Results for Treating Desmoid Tumors

Patients with progressive, symptomatic, or recurrent desmoid tumors who received sorafenib have significantly improved progression-free survival (PFS) rates at 1 and 2 years compared with patients who received placebo, according to the results of a recent phase 3 trial.

Desmoid tumors are neoplasms that originate from connective tissues, with common sites such as the abdominal wall, mesentery, and neurovascular bundle of the extremities. Although desmoid tumors normally do not metastasize, with the exception in Gardner syndrome, patients may have compromised vital organs, bowel obstruction, severe pain, and swelling.

There are numerous systemic treatment options that have been used for desmoid tumors: hormonal therapy, cytotoxic chemotherapy, and tyrosine kinase inhibitors; however, no standard of care has been accepted. In a retrospective analysis, sorafenib had emerged as a potential treatment option, with response rates of 25% and a tolerable safety profile. With these promising results already present, the current phase 3 trial sought to verify and evaluate the safety and efficacy of sorafenib for patients with desmoid tumors.

Eighty-seven patients with progressive, symptomatic, or recurrent desmoid tumors were enrolled in this trial and were randomly assigned to receive either sorafenib (400 mg daily) or placebo in a 2:1 ratio—50 patients received sorafenib and 37 patients received placebo. Treatment continued until disease progression, unacceptable adverse effects, or withdrawal of consent.

After a median follow-up period of 27.2 months, the PFS rates at 1 year were 89% and 46% for patients receiving sorafenib and placebo, respectively. PFS rates at 2 years were 81% and 36%, respectively (hazard ratio [HR], 0.13; 95% CI, 0.05-0.31; P < .0001). Of the patients in the sorafenib group, 12% of them had disease progression compared with 63% of those in the placebo group.

The objective response rate was 33% in the sorafenib group and 20% in the placebo group. Changes in the sum of target lesions also favored the sorafenib group (—26% vs –12% in the placebo group). Median time to response was 9.6 months in the sorafenib group and 13.3 months in the placebo group.

The most common cause for dose reductions in the sorafenib group were skin disorders, including rashes, pruritis, and palmar-plantar erythrodysesthesia syndrome. Discontinuation of treatment occurred in 20% of the patients receiving sorafenib and 0% of the patients receiving placebo. Grade 4 events that investigators suspected to be caused by sorafenib included thrombocytopenia and anemia, 2% each.

Based on the results of this phase 3 trial, investigators concluded that sorafenib was a safe and effective treatment option for patients with desmoid tumors. From the advantageous PFS rates and antitumor activity that it exerts, sorafenib may have a place in desmoid tumor as first-line or as subsequent therapy, they said.

Reference

Gounder MM, Mahoney MR, Van Tine BA et al. Sorafenib for advanced and refractory desmoid tumors. N Engl J Med. 2018;379(25):2417-2428. doi: 10.1056/NEJMoa1805052.