Vismodegib in the Treatment of Basal Cell Carcinoma: Indications for Clinical Practice

Abstract

Basal cell carcinoma (BCC) is a frequent skin cancer which can cause substantial morbidity due to its location on the face, its frequency of relapse and its capacity to invade local tissues. The primary treatment of BCC usually involves surgery or radiotherapy. In patients who have exhausted surgical and radiotherapy options or with metastatic BCC, guidelines recommend the use of the Hedgehog pathway inhibitor vismodegib. This molecule is indicated for the treatment of adults with metastatic BCC, or with locally advanced BCC which has recurred following surgery or who are not eligible to surgery or radiation. This paper aims to provide suggestions on the optimal management of BCC patients treated with vismodegib in clinical practice, according to the large experience gained by a group of Italian dermatologists and oncologists. In particular, the focus of this paper will be on the monitoring of patients and the management of adverse events.

Tailored Toxicity-Driven Administration of Vismodegib in Patients With Multiple or Locally Advanced Basal Cell Carcinoma: A Pilot Analysis

“…However, this evaluation was performed, in line with our practice, only 2 months after the initiation of therapy, and three patients progressed shortly afterwards. In line with previous literature (16)(17)(18), all the patients in our series with controlled disease showed cramps or dysgeusia over the course of therapy, requiring interruption of the standard therapy. We considered the possibility of switching to an intermittent vismodegib schedule for all these patients, consisting of 4-week courses with 2-week interruptions in between.…”

“…Although vismodegib is widely used for the treatment of advanced BCC, further research has been advocated on its effectiveness and treatment schedules in clinical practice (12,13). In particular, some concerns on the use of vismodegib have been raised due to the frequent onset of AEs associated with this molecule, especially cramps and dysgeusia (16)(17)(18). The onset of these events may lead to treatment interruption and, potentially, to tumor progression.…”

“…In particular, adverse events (AEs) are not uncommon with the chronic use of vismodegib, especially at the gastrointestinal and musculoskeletal level, and often lead to early interruption of treatment (16)(17)(18). This has important clinical consequences because vismodegib, in some cases, does not eradicate the disease, and the tumor may, therefore, regrow when therapy is definitively interrupted.…”

Phase I, multicenter, open‐label, dose‐escalation study of sonidegib in Asian patients with advanced solid tumors

“…Interestingly, increased concentrations of CK were also reported in a patient treated with vismodegib. Muscle spasms are reported in approximately 70% of patients treated with vismodegib . It is known that both vismodegib and sonidegib are canonical Hh signaling inhibitors.…”

“…Muscle spasms are reported in approximately 70% of patients treated with vismodegib. (16) It is known that both vismodegib and sonidegib are canonical Hh signaling inhibitors. However, vismodegib also activates a non-canonical SMO/Ca 2+ /AMP-activated protein kinasedependent signaling cascade leading to a Warburg-like catabolic reprograming, which sonidegib does not, and as a result SMO-dependent Ca 2+ induction does not induce metabolic rewiring.…”