Toremifene in desmoid fibromatosis: Prospective phase 2 study of two dose levels

Summary

Background: Toremifene has been used for many years in desmoid-type fibromatosis (DF). In order to test the dose efficacy and assess activity and safety of toremifene in DF, we conducted this prospective phase 2 study (NCT02353429). Patients and methods: Patients with progressing sporadic primary or recurrent DF were enrolled. At study entry, patients received oral toremifene daily at a dose of 60 mg. In case of progression the dose was escalated to 180 mg daily. Descriptive statistics were used to summarize the patient's characteristics. The clinical benefit was evaluated by comparing sequentially measured paired failure times within each treated patient, namely time to progression after the 60 mg toremifene dose (TTP1) versus the (possibly censored) time to progression after the 180 mg toremifene dose (TTP2). Results: Twenty-two patients were enrolled. Two patients did not switch to 180 mg. The majority of patients (60%) entered the study for radiological dimensional progression. The 6 and 12 months progression-free survival (PFS) probability was 14.4% (95% CI, 5.1-41.1) and 4.8% (95% CI, 0.7-32.6) for patients receiving 60 mg compared with 72.0% (95% CI, 54.2-96.2) and 52.5% (95% CI, 33.1-83.3) for those receiving 180 mg. Overall, 16 of 20 patients experienced a longer time to progression after dose escalation (TTP2 ≥ TTP1). A binomial exact test showed that TTP2 was significantly higher than TTP1 (GMI 80.0%; 95% CI, 60.0-100; p = 0.0059), indicating that the study's primary objective was met. No toremifene-related serious adverse events were observed. Conclusion: Toremifene at 60 mg daily is ineffective in this patient population. However, clinical benefit was observed at 180 mg in selected cases. Further prospective studies are warranted to explore the potential role of toremifene for selected patients.