The use of vismodegib to shrink keratocystic odontogenic tumors in patients with basal cell nevus syndrome

Abstract

Importance: Keratocystic odontogenic tumors (KCOTs) of the jaw affect more than 65% of patients with basal cell nevus syndrome (BCNS). Surgery frequently causes facial disfigurement and is not always curative. Most BCNS-related and some sporadic KCOTs have malignant activation of the Hedgehog signaling pathway.

Observations: We examined the effect of vismodegib (an oral Hedgehog pathway inhibitor) on KCOT size in patients with BCNS enrolled in a clinical trial testing vismodegib for basal cell carcinoma prevention (NCT00957229), using pretreatment and posttreatment magnetic resonance imaging. Four men and 2 women had pretreatment KCOTs (mean longest diameter, 2.0 cm; range, 0.7-3.3 cm), occurring primarily in the mandible. Patients were treated with vismodegib, 150 mg/d, for a mean (SD) of 18.0 (4.8) months (range, 11-24 months). Four patients experienced a size reduction and 2 had no change. Vismodegib reduced the mean longest diameter of KCOTs in all patients by 1.0 cm (95% CI, 0.03-1.94; P = .02) or 50% from baseline. We observed no enlargement of existing KCOTs or new KCOT development.

Conclusions and relevance: Vismodegib shrinks some KCOTs in patients with BCNS and may offer an alternative to surgical therapy. These effects were maintained for at least 9 months after drug cessation in 1 patient. Further studies assessing long-term efficacy and optimal maintenance regimens should be performed.

Conflict of interest statement

All other relationships: JYT and EE are consultants for Genentech. EE is also consultant for Novartis and owns stock options in Curis and Infinity. The authors disclose no other potential conflicts of interest.

Figures

Figure 1

CONSORT diagram. A CONSORT flow diagram of patient selection highlighting reasons for exclusion from the case series, as well as, baseline and post-treatment MRI results.

Figure 2

MRI images of subject 4. Serial sagittal T2 weighted MRI images demonstrating the size change in the left maxillary KCOT (red arrows) from A) baseline B) after 11 months of vismodegib and C) 9 months after drug discontinuation.