In another study evaluating vismodegib in 104 patients with advanced BCC, researchers observed non-BCC malignancies in 6 patients, including 2 cases each of malignant melanoma and SCC.3 Yet another study of vismodegib in 499 patients with locally advanced or metastatic BCC revealed 12 cases of cutaneous SCC.4
While cutaneous SCCs developing during treatment with vismodegib have been reported, it is unclear whether these tumors are a result of hedgehog signaling pathway inhibition or a general increased risk for dermatologic malignancies in patient populations.1,5-10
In a trial assessing the safety and efficacy of 2 difference doses of sonidegib in patients with locally advanced or metastatic BCC, investigators observed secondary malignancies in 6% of the 79 patients who received the approved 200 mg dose of sonidegib. New malignant disease included 3 cases of SCC and 1 case of malignant melanoma.11
“There are no specific guidelines for monitoring patients during hedgehog pathway inhibitor therapy,” noted Dr Zalaudek. “I would, however, recommend carrying out a total-body skin examination at least every 3 months during treatment.
“In addition, patients should be advised to seek immediate consultation in the case of newly developing and fast growing pigmented and non-pigmented nodules.”
Although evidence suggests that secondary skin malignancies in patients treated with smoothened inhibitors is most likely to occur in patients treated with vismodegib, Dr Zalaudek suggested that patients receiving any smoothened inhibitor should be monitored carefully. Comparative data are, however, needed.
- Giuffrida R, Kashofer K, Dika E, et al. Fast growing melanoma following treatment with vismodegib for locally advanced basal cell carcinomas: report of two cases. Eur J Cancer. 2018 Jan 16. doi: 10.1016/j.ejca.2017.11.031 [Epub ahead of print]
- Mohan SV, Chang J, Li S, Henry AS, Wood DJ, Chang AL. Increased risk of cutaneous squamous cell carcinoma after vismodegib therapy for basal cell carcinoma. JAMA Dermatol. 2016;152(5):527-32.
- Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366:2171-9.
- Basset-Seguin N, Hauschild A, Grob JJ, et al. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol. 2015;16(6):729-39.
- Poulalhon N, Dalle S, Balme B, Thomas L. Fast-growing cutaneous squamous cell carcinoma in a patient treated with vismodegib. Dermatology. 2015;230(2):101-4.
- Saintes C, Saint-Jean M, Brocard A, et al. Development of squamous cell carcinoma into basal cell carcinoma under treatment with vismodegib. J Eur Acad Dermatol Venereol. 2015;29(5):1006-9.
- Zhu GA, Sundram U, Chang AL. Two different scenarios of squamous cell carcinoma within advanced Basal cell carcinomas: cases illustrating the importance of serial biopsy during vismodegib usage. JAMA Dermatol. 2014;150(9):970-3.
- Orouji A, Goerdt S, Utikal J, Leverkus M. Multiple highly and moderately differentiated squamous cell carcinomas of the skin during vismodegib treatment of inoperable basal cell carcinoma. Br J Dermatol. 2014;171(2):431-3.
- Iarrobino A, Messina JL, Kudchadkar R, Sondak VK. Emergence of a squamous cell carcinoma phenotype following treatment of metastatic basal cell carcinoma with vismodegib. J Am Acad Dermatol. 2013;69(1):e33-4.
- Aasi S, Silkiss R, Tang JY, et al. New onset of keratoacanthomas after vismodegib treatment for locally advanced basal cell carcinomas: a report of 2 cases. JAMA Dermatol. 2013;149(2): 242-3.
- Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015;16(6):716-28.