Gene-Related Response of Basal Cell Carcinoma to Biologic Treatment with Vismodegib.

We aimed to characterise the response of locally advanced basal cell carcinoma (BCC) to systemic treatment with Vismodegib, a Hedgehog pathway inhibitor, by changes in the expression levels of Hedgehog pathway genes. Data were collected prospectively on 12 patients treated systemically for locally advanced BCC. Biopsy samples taken on admission and after treatment cessation were analysed pathologically and with the NanoString nCounter system to quantify the expression of 40 Hedgehog signaling pathway genes. Findings were compared before and after treatment, between complete and partial responders, and with localised BCC samples from 22 patients. Sixteen Hedgehog pathway genes changed significantly from before to after treatment. GAS1 was the only gene with a significantly different expression at baseline between complete responders (6 patients) and partial responders (4 patients) to Vismodegib (P = 0.014). GAS, GLIS2 and PRKACG1 showed different expression before treatment between the locally advanced and localised BCCs. The baseline expression level of GAS1 appears to be predictive of the response of locally advanced BCC to systemic Vismodegib treatment. A change in expression of many Hedgehog pathway genes, albeit expected by the known activity of Vismodegib, may nevertheless serve as an indicator of the response potential of the tumour.

Efficacy of Vismodegib for the Treatment of Orbital and Advanced Periocular Basal Cell Carcinoma.

PURPOSE: To evaluate the effectiveness of vismodegib, a Hedgehog pathway inhibitor, in treating orbital and advanced periocular basal cell carcinoma (BCC) in Israeli multidisciplinary medical centers. DESIGN: Retrospective case series. METHODS: Background, treatment, and outcome data were retrospectively collected from the medical records of all patients with locally advanced and metastatic orbital or periocular BCC treated with vismodegib in 2012-2017 at 2 tertiary medical centers. RESULTS: The cohort included 21 patients (16 male) of median age 76 years with periocular (n=6) or orbital (n=15) BCC. Median duration of treatment was 9 months, with follow-up of 26 months (range 9-60 months) overall and 17 months after treatment cessation. Clinical response was complete in 10 patients, partial in 10 patients, and stable in 1 patient. Among the complete responders, 5 maintained a complete response at 16 months, and 3 who stopped treatment had a recurrence 8 months later. Almost all treatment-related adverse reactions were graded 1 or 2 (low-grade). The most common grade 1 or 2 complications were muscle spasm (76%), followed by dysgeusia (57%), alopecia (47%), weight loss (47%) and decreased appetite (19%). The only grade 3 or 4 adverse event was hepatotoxicity (10%). Eight patients discontinued treatment because of side effects. Five patients died, most from reasons unrelated to vismodegib therapy, except for 1 patient who died from possibly treatment-related sepsis (grade 5 adverse event). CONCLUSIONS: To our knowledge, this is the only study generated outside the United States and Europe, and it represents the largest study to date on vismodegib therapy for locally advanced periocular BCC. Treatment according to an individualized maximally tolerated dose may achieve a comparable response to the ERIVANCE protocol. Longer-term studies are needed to assess prognosis.

Vismodegib for radiation-induced multiple basal cell carcinomas (BCCs) of the scalp.

BACKGROUND: Vismodegib has been approved for treatment of locally advanced or metastatic basal cell carcinoma (BCC). Its use for postirradiation multiple BCCs has not yet been reported. OBJECTIVE: We sought to investigate the effectiveness and safety of vismodegib for the treatment of recurrent radiation-induced multiple BCCs. METHODS: Patients with recurrent multiple BCCs treated with vismodegib and a history of exposure to radiation treatment were followed up prospectively at a tertiary dermato-oncology clinic during a 19-month period. RESULTS: Eight patients met the study criteria. Mean duration of vismodegib treatment was 29 weeks (range 2-52), and of follow-up, 34 weeks (range 8-64). Drug tolerability was acceptable in 7 patients, of whom 4 showed a partial response and 3 had stable disease. In 1 patient, vismodegib was discontinued soon after its initiation because of a severe drug-induced eruption. LIMITATIONS: Small sample size and short follow-up time are limitations. CONCLUSION: Vismodegib holds promise for the treatment of the subpopulation of patients with radiation-induced multiple BCCs in whom therapeutic options have so far been limited.

Vismodegib as a neoadjuvant treatment to Mohs surgery for aggressive basal cell carcinoma.

BACKGROUND: Vismodegib, a hedgehog pathway inhibitor has been recently introduced as an oral therapy for locally advanced and metastatic basal cell carcinoma. Although treatment of patients with basal cell carcinoma with vismodegib has been associated with partial or complete clinical response, it is still unclear if it is also associated with histological cure. PATIENTS: Two patients with 3 large and aggressive basal cell carcinomas were treated with Vismodegib for 6 months. The treatment was followed by Mohs micrographic surgery. RESULTS: Two tumors disappeared clinically and one was reduced dramatically in its size following treatment with vismodegib. Mohs surgery in all three tumors revealed residual islands of BCC although margins were cleared at the end of surgery. CONCLUSIONS: Neoadjuvant therapy with vismodegib for 6 months prior to Mohs surgery was effective in reducing the size of primary and recurrent aggressive basal cell carcinoma. However, residual tumor nests were found during surgery. Further larger studies are needed to evaluate the efficacy of Vismodegib as a neoadjuvant treatment prior to Mohs surgery.