Clinical outcomes of sunitinib (Su) for patients (pts) with desmoid tumors (DT)

Summary

The incidence of DT is steadily increasing in pts affected by familial adenomatous polyposis (FAP) and represents the first cause of death for pts who underwent preventive proctocolectomy. Currently, there is no standard therapy for DT and Tamoxifen (20 mg once daily) + Meloxicam (15 mg once daily) (TM) is the most commonly used regimen in clinical routine. We sought to evaluate the efficacy of Su, the most active PDGFR TKI, as first-line therapy for pts with DT. In this phase II IRB approved prospective study, pts with progressive, symptomatic, or recurrent DT were randomized to receive either Su (52 mg once daily) or TM. The primary end point was progression-free survival, defined as time from treatment start to clinical or radiological progression, whichever came first, at 2 years (2yr-PFS). Of the 32 pts enrolled, 22 received Su and 10 TM. In both groups, median age at diagnosis was 43.5 years. No OR was observed in the TM group. In the Su group, 17 pts had a partial response and 5 stable disease and the ORR was 75% (95% CI, 50 to 100). At a median follow-up of 27 months, the 2yr-PFS was 81% (95% CI, 69-96) and 36% (95% CI, 22-57) in the Su cohort and TM cohort, respectively (HR = 0.13; 95% CI, 0.05- 0.31; P<0.001). The median ttOR among pts who had an OR was 24 months. In the TM group, no toxicity was observed. The most frequently reported AE in the Su group were grade 1 or 2 hypothyroidism (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). (HR: 0.260; p = 0.0035). All AE responded to dose reduction (37.5 mg). In a cohort of pts with progressive, recurrent, or symptomatic DT, Su seems to be well tolerated and improve 2yr-PFS and OR rate compared with TM therapy. Further prospective studies with larger samples are needed to verify these results.