A phase II trial of perioperative oral itraconazole for the management of low risk basal cell carcinoma.

Abstract

9582 Background: Recently, new treatment options have emerged for advanced basal cell carcinoma (BCC), including oral Hedgehog pathway inhibitors like Vismodegib. Itraconazole has also shown promising clinical activity in these cases by targeting the SMO receptor. This study aimed to assess the clinical and molecular efficacy of oral Itraconazole in BCC patients with low-risk disease. Methods: Patients with localized BCC who were eligible for surgical excision were enrolled. They received 200 mg of Itraconazole twice daily for 60 days prior to resection. Clinical assessments were based on the RECIST 1.1 criteria, with target lesions measuring at least 10 mm following a confirmatory biopsy. Molecular markers associated with cellular activity and angiogenesis (Ki67, GLI, CD105) were evaluated using immunohistochemical staining. Adverse effects were graded according to NCI-CTC v4. Results: A total of 26 patients were treated, with 61% female and a mean age of 62 years. The most common BCC subtype was nodular (54%), and the most frequent tumor location was the trunk (65%). Patients presented with stable disease (92%), partial response (4%), and complete response (4%). Notably, no disease progression occurred during the treatment period, and all patients underwent the planned surgical excision. The median tumor diameter prior to treatment was 14 mm (range: 11–16 mm), and after treatment, it was 13 mm (range: 11–15 mm). This reduction was statistically significant, as determined by the Wilcoxon test (p < 0.0001). Additionally, biological activity of Itraconazole was demonstrated through the measurement of Ki67, GLI, and CD105. The percentage of the stained area for CD105 or Endoglin decreased significantly following Itraconazole treatment, from 0.11 [0.01–1.86] to 0.03 [0.00–0.22], with this reduction also being statistically significant (p ≤ 0.0001). Conclusions: Preoperative oral Itraconazole demonstrated both clinical and molecular activity in localized, low-risk BCC lesions, with no patients showing disease progression and two patients exhibiting partial and complete responses, respectively. The median tumor diameter significantly decreased after the treatment period. In addition to the reduction in tumor size, there was a notable decrease in the expression of CD105, marking the first study to demonstrate this correlation in this context. Endoglin, a well-established marker for endothelial cell proliferation, particularly in angiogenesis in regenerating tissues or inflamed tumors, underscores the antiangiogenic potential of Itraconazole. These findings align with previously published results and suggest that oral Itraconazole could be a promising candidate for managing low-risk BCC, while also opening the opportunity for further investigation in advanced disease settings. Clinical trial information: NCT03972748 .