JOURNAL of
ONCOLOGICAL
SCIENCES

ORIGINAL RESEARCH ARTICLE

Vismodegib for Patients with Advanced Basal Cell Carcinoma: One Center’s Experience
Received Date : 26 Oct 2019
Accepted Date : 18 Feb 2020
Available Online : 17 Apr 2020
Doi: 10.37047/jos.2019-71992 - Article's Language: EN
J Oncol Sci. 2020;6(1):5-9
This is an open access article under the CC BY-NC-ND license
ABSTRACT
Objective: Vismodegib is the first-in-class oral small molecule inhibitor in advanced basal cell carcinoma (BCC). We herein report the treatment experience with vismodegib at the oncology department of the Gaziantep university medical faculty. Material and Methods: This was a retrospective analyze of consecutive 15 BCC patients with locally advanced and metastatic stage between August 2016 and June 2019. While the primary endpoint was progression free survival, secondary endpoints were efficacy and toxicity. Results: The mean duration of treatment was 9.1 months on vismodegib (range, 0.97-28.60 months) with a lengthy median follow-up time of 17.6 months. The overall response rate (ORR) was 73.3%, with 20% (n=3) of patients having complete response, 53.3% (n=8) having partial response and 20% (n=3) exhibiting stable disease. Progression was observed in 6.7% of the patients. Eight patients (%53) discontinued the treatment. The most common reason for discontinuation was drug side-effects (%53). Mainly side-effects (all grades) were fatigue (80%), muscle cramps (60%), loss of appetite (53.3%) and dysgeusia (46.6%). The median PFS was 9.66 months (95% CI; 2.05-17.28). Conclusion: Our PFS results seem contradictory to the reports indicating longer PFS with vismodegib, in the lack of difference in response rate. This study also confirmed that vismodegib has notable adverse effects in agreement with previous reports. The most frequently encountered problem was high dropout rates of treatment. It seems essential to manage toxicity and provide coping strategies for adverse effects in daily clinical practice. It was considered higher dropout from treatment may be associated with shortened PFS.
REFERENCES
  1. Roenigk RK, Ratz JL, Bailin PL, Wheeland RG. Trends in the presentation and treatment of basal cell carcinomas. J Dermatol Surg Oncol. 1986;12(8):860-865. [Crossref]  [PubMed] 
  2. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012. JAMA Dermatol. 2015;151(10):1081-1086. [Crossref]  [PubMed] 
  3. Buettner PG, Raasch BA. Incidence rates of skin cancer in Townsville, Australia. Int J Cancer. 1998;78(5):587-593. [Crossref] 
  4. Muzic JG, Schmitt AR, Wright AC, et al. Incidence and trends of basal cell carcinoma and cutaneous squamous cell carcinoma: a population-based study in olmsted county, Minnesota, 2000 to 2010. Mayo Clin Proc. 2017;92(6):890-898. [Crossref]  [PubMed] 
  5. Verkouteren JAC, Ramdas KHR, Wakkee M, Nijsten T. Epidemiology of basal cell carcinoma: scholarly review. Br J Dermatol. 2017;177(2):359-372. [Crossref]  [PubMed] 
  6. Wysong A, Aasi SZ, Tang JY. Update on metastatic basal cell carcinoma: a summary of published cases from 1981 through 2011. JAMA Dermatol. 2013;149(5):615-616. [Crossref]  [PubMed] 
  7. Tanese K, Emoto K, Kubota N, Fukuma M, Sakamoto M. Immunohistochemical visualization of the signature of activated Hedgehog signaling pathway in cutaneous epithelial tumors. J Dermatol. 2018;45(10):1181-1186. [Crossref]  [PubMed] 
  8. de Zwaan SE, Haass NK. Genetics of basal cell carcinoma. Australas J Dermatol. 2010;51(2):81-94. [Crossref]  [PubMed] 
  9. Bakshi A, Chaudhary SC, Rana M, Elmets CA, Athar M. Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond. Mol Carcinog. 2017;56(12):2543-2557. [Crossref]  [PubMed]  [PMC] 
  10. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179. [Crossref]  [PubMed]  [PMC] 
  11. Basset-Séguin N, Hauschild A, Kunstfeld R, et al. Vismodegib in patients with advanced basal cell carcinoma: primary analysis of STEVIE, an international, open-label trial. Eur J Cancer. Nov 2017;(86):334-348. [Crossref]  [PubMed] 
  12. Xie P, Lefrançois P. Efficacy, safety, and comparison of sonic hedgehog inhibitors in basal cell carcinomas: a systematic review and meta-analysis. J Am Acad Dermatol. 2018;79(6):1089-1100. [Crossref]  [PubMed] 
  13. Kim DJ, Kim J, Spaunhurst K, et al. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol. 2014;32(8):745-751. [Crossref]  [PubMed] 
  14. McCusker M, Basset-Seguin N, Dummer R, et al. Metastatic basal cell carcinoma: prognosis dependent on anatomic site and spread of disease. Eur J Cancer. 2014;50(4):774-783. [Crossref]  [PubMed] 
  15. Palle K, Mani C, Tripathi K, Athar M. Aberrant GLI1 activation in DNA damage response, carcinogenesis and chemoresistance. Cancers (Basel). 2015;7(4):2330-2351. [Crossref]  [PubMed]  [PMC]