A Review of the Risk of Cutaneous Squamous Cell Carcinoma after Vismodegib Therapy
Main Article Content
Keywords
skin cancer, squamous cell carcinoma, basal cell carcinoma, vismodegib
Abstract
Since vismodegib’s approval for advanced or metastatic basal cell carcinoma, there has been concern over vismodegib’s potential to induce secondary neoplasms of the skin, such as cutaneous squamous cell carcinoma (cSCC). In this article, we provide a comprehensive review of the literature on vismodegib’s relationship to cSCC. A systematic search of PubMed and Ovid MEDLINE was performed with terms “vismodegib” AND “squamous cell carcinoma.” Studies ranged from May 2013 to January 2022 and 25 articles were ultimately included. In total, of the 2576 patients included in the review, there were 197 cSCCs reported. Numerous reports have published conflicting findings. While one retrospective cohort study did find an increased risk, additional studies have found that the rates of cSCC are comparable between those exposed and those not exposed. Because a causal relationship between vismodegib and cSCC has not been proven, its use should not be avoided due to concerns of causing cSCC. However, patients treated with vismodegib should be closely monitored by dermatologists to evaluate for any suspicious changes. Large-scale, prospective, multi-center studies should be performed to definitively determine the risk of cSCC and vismodegib. It has been proposed that vismodegib may select for tumor cells utilizing the Ras/MAPK pathways.
References
2. 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):527-532. doi:10.1001/jamadermatol.2015.4330
3. Chang AL, Solomon JA, Hainsworth JD, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol. 2014;70(1):60-69. doi:10.1016/j.jaad.2013.09.012
4. Sekulic A, Yoo S, Kudchadkar R, et al. Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry. PLoS One. 2022;17(1):e0262151. Published 2022 Jan 14. doi:10.1371/journal.pone.0262151
5. Li S, Chang AL. Study on the Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma-Reply. JAMA Dermatol. 2016;152(10):1173. doi:10.1001/jamadermatol.2016.2429
6. Puig S, Sampogna F, Tejera-Vaquerizo A. Study on the Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma: Not a Case-Control Study. JAMA Dermatol. 2016;152(10):1172-1173. doi:10.1001/jamadermatol.2016.2428
7. Gjersvik P. Study on the Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma: Not a Case-Control Study. JAMA Dermatol. 2016;152(10):1172. doi:10.1001/jamadermatol.2016.2427
8. 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):1006-1009. doi:10.1111/jdv.12526
9. 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-e34. doi:10.1016/j.jaad.2013.01.023
10. Poulalhon N, Dalle S, Balme B, Thomas L. Fast-growing cutaneous squamous cell carcinoma in a patient treated with vismodegib. Dermatology. 2015;230(2):101-104. doi:10.1159/000368350
11. Ransohoff KJ, Tang JY, Sarin KY. Squamous Change in Basal-Cell Carcinoma with Drug Resistance. N Engl J Med. 2015;373(11):1079-1082. doi:10.1056/NEJMc1504261
12. Rübben A, Hilgers RD, Leverkus M. Hedgehog Blockade for Basal Cell Carcinoma: Coming at a (Secondary Neoplastic) Price. JAMA Dermatol. 2016;152(5):521-523. doi:10.1001/jamadermatol.2015.5239
13. Axelson M, Liu K, Jiang X, et al. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. Clin Cancer Res. 2013;19(9):2289-2293. doi:10.1158/1078-0432.CCR-12-1956
14. 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):431-433. doi:10.1111/bjd.12840
15. 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):242-243. doi:10.1001/jamadermatol.2013.1798
16. Kuonen F, Huskey NE, Shankar G, et al. Loss of Primary Cilia Drives Switching from Hedgehog to Ras/MAPK Pathway in Resistant Basal Cell Carcinoma. J Invest Dermatol. 2019;139(7):1439-1448. doi:10.1016/j.jid.2018.11.035
17. Otsuka A, Dreier J, Cheng PF, et al. Hedgehog pathway inhibitors promote adaptive immune responses in basal cell carcinoma. Clin Cancer Res. 2015;21(6):1289-1297. doi:10.1158/1078-0432.CCR-14-2110
18. Zhao X, Ponomaryov T, Ornell KJ, et al. RAS/MAPK Activation Drives Resistance to Smo Inhibition, Metastasis, and Tumor Evolution in Shh Pathway-Dependent Tumors. Cancer Res. 2015;75(17):3623-3635. doi:10.1158/0008-5472.CAN-14-2999-T
19. Lee JJ, Kroshinsky D, Hoang MP. Cutaneous Reactions to Targeted Therapy. Am J Dermatopathol. 2017;39(2):67-82. doi:10.1097/DAD.0000000000000504
20. 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):970-973. doi:10.1001/jamadermatol.2014.583
21. Chang ALS. Commentary on Development of Basal Cell Carcinoma With Squamous Differentiation During Vismodegib Treatment. Dermatol Surg. 2017;43(7):991-992. doi:10.1097/DSS.0000000000001059
22. Danhof R, Lewis K, Brown M. Small Molecule Inhibitors of the Hedgehog Pathway in the Treatment of Basal Cell Carcinoma of the Skin. Am J Clin Dermatol. 2018;19(2):195-207. doi:10.1007/s40257-017-0319-4
23. Li S, Chang AL. Study on the Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma-Reply. JAMA Dermatol. 2016;152(10):1173. doi:10.1001/jamadermatol.2016.2429
24. Feigenbaum L, Scott BL, Moye MS, Nijhawan RI. Development of Basal Cell Carcinoma With Squamous Differentiation During Vismodegib Treatment. Dermatol Surg. 2017;43(7):989-991. doi:10.1097/DSS.0000000000001012
25. Bancalari B, Llombart B, Serra-Guillén C, et al. Histologic Changes During Treatment With Vismodegib in Locally Advanced Basal Cell Carcinoma: A Series of 19 Cases. Am J Dermatopathol. 2019;41(10):711-717. doi:10.1097/DAD.0000000000001384
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Creative Commons Attribution (CC BY): lets others distribute and copy the article, to create extracts, abstracts, and other revised versions, adaptations or derivative works of or from an article (such as a translation), to include in a collective work (such as an anthology), to text or data mine the article, even for commercial purposes, as long as they credit the author(s), do not represent the author as endorsing their adaptation of the article, and do not modify the article in such a way as to damage the author's honor or reputation.
Authors retain copyright in their work and license the publisher to publish the content. The publisher is the National Society for Cutaneous Medicine, with production and publishing support provided by OJS, Open Journal Systems,see https://pkp.sfu.
Prior to January 2022, authors transferred copyright to the National Society for Cutaneous Medicine. However, all articles are freely available to anyone in the world. There are no subscription fees, page charges, or article processing charges.