Sorafenib may slow desmoid tumour progression
A once-daily dose of sorafenib may improve progression-free survival (PFS) in patients with desmoid tumours, a condition that currently has no standard-of-care treatment, according to a phase III trial.
Participants were 87 adults (median age 37 years, 69 percent female, 80 percent Caucasian) with progressive, symptomatic, or recurrent desmoid tumours who were randomized to receive oral sorafenib (400 mg once/day; n=50) or placebo (n=37) until disease progression, unacceptable toxicity, or consent withdrawal. Patients underwent magnetic resonance imaging or computed tomography at baseline and every 8 weeks and were followed up for a median 27.2 months.
The estimated PFS rate was significantly higher among sorafenib than placebo recipients (81 percent vs 36 percent at 2 years), with an 87 percent lower risk of disease progression or death among sorafenib compared with placebo recipients (hazard ratio, 0.13, 95 percent confidence interval, 0.05–0.31; p<0.001). [N Engl J Med 2018;379:2417-2428]
“This is a truly remarkable outcome,” said senior author Professor Gary K. Schwartz from the NewYork-Presbyterian/Columbia University Irving Medical Center in New York, US. “In fact, we have never seen results like this in the treatment of desmoid tumours.”
Of the 28 trial participants who experienced disease progression, six had received sorafenib, while 22 had received placebo.
Patients on placebo were permitted to cross over to receive sorafenib in the case of progression of disease; pre-crossover objective response rate was 33 and 20 percent among sorafenib and placebo recipients, respectively. Among responders, median time to objective response was 9.6 and 13.3 months among sorafenib and placebo recipients, respectively, and the mean best percentage change in target lesion sum was -26 and -12 percent, respectively.
Thirty-one and 11 percent of sorafenib and placebo recipients, respectively, had their treatment doses reduced due to toxicity, with skin disorders the main reason for dose reduction among sorafenib recipients. Twenty percent of sorafenib recipients discontinued treatment due to adverse events (AEs) compared with none on placebo. Treatment-related grade 3 AEs affected 29 and 14 percent of sorafenib and placebo recipients, respectively, with thrombocytopenia (2 percent) and anaemia (2 percent) sorafenib-related grade 4 AEs. Nausea, diarrhoea, rash, and hand-foot syndrome occurred more frequently among sorafenib compared with placebo recipients, with grade 1–2 rash (73 percent), fatigue (67 percent), hypertension (55 percent), and diarrhoea (51 percent) the most frequently occurring AEs among sorafenib recipients.
“[D]esmoids are locally aggressive and often painful tumours for which there are no effective therapies. Sorafenib is an oral agent that provides a new means to directly target the ability of desmoid tumours to grow,” said Schwartz.
However, the researchers also highlighted the rate of disease regression which occurred in 20 percent of patients on placebo, which “[supported] an initial period of observation in patients with newly diagnosed desmoid tumours”.
“On the basis of the predictable toxic-effects profile and substantial PFS advantage conferred by sorafenib, the drug has antitumour activity as first-line therapy or as subsequent therapy for desmoid tumours,” they said, calling for further investigation into assessing the impact of treatment on “patient experience”, taking into account pain and quality of life outcomes, as well as the mechanism of action of sorafenib and its optimal treatment duration for desmoid tumours.