Sonidegib in the Treatment of Locally Advanced Basal Cell Carcinoma: A Retrospective Study
DOI:
https://doi.org/10.2340/actadv.v102.1995Keywords:
basal cell carcinoma, sonidegib, hedgehog pathway inhibitor, locally advancedAbstract
Sonidegib, a hedgehog pathway inhibitor, is indicated for treatment of locally advanced basal cell carcinoma, based on the results of the BOLT study. However, to date, no real-world study of sonidegib has been reported. An observational, retrospective, single-centre study (PaSoS study) was conducted. The primary objective was to evaluate the efficacy of sonidegib for treatment of locally advanced basal cell carcinoma in a real-world setting. Secondary objectives included modalities of use, tolerability, tumour evolution, and management after discontinuation. A total of 21 patients treated with sonidegib were included from March 2018 to January 2021. The median follow-up was 18.7 months and median exposure 7.0 months. Objective response (OR) rate was 81.0% (n = 17) including 6 (29%) patients with a complete response (CR). Disease control rate was 100%. First tumour response was rapid, with a median time of 2.3 months. Nine (43%) patients underwent surgery after sonidegib discontinuation, and no relapse was observed. All the patients experienced at least 1 adverse event (AE). Muscle spasms were the most frequent AE (n = 14; 67%), followed by dysgeusia (n = 8; 38%) and alopecia (n = 12; 57%). The efficacy and safety profile of sonidegib in this first-to-date real-life trial are consistent with prior results. Overall, real-world evidence corroborated sonidegib efficacy and tolerability as a first-line treatment for locally advanced basal cell carcinoma.
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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209-249.
https://doi.org/10.3322/caac.21660 DOI: https://doi.org/10.3322/caac.21660
Ridky TW. Nonmelanoma skin cancer. J Am Acad Dermatol 2007; 57: 484-501.
https://doi.org/10.1016/j.jaad.2007.01.033 DOI: https://doi.org/10.1016/j.jaad.2007.01.033
Villani A, Fabbrocini G, Costa C, Scalvenzi M. Sonidegib: safety and efficacy in treatment of advanced basal cell carcinoma. Dermatol Ther (Heidelb) 2020; 10: 401-412.
https://doi.org/10.1007/s13555-020-00378-8 DOI: https://doi.org/10.1007/s13555-020-00378-8
Peris K, Fargnoli MC, Garbe C, Kaufmann R, Bastholt L, Seguin NB, et al. Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines. Eur J Cancer 2019; 118: 10-34.
https://doi.org/10.1016/j.ejca.2019.06.003 DOI: https://doi.org/10.1016/j.ejca.2019.06.003
Work G, Invited R, Kim JYS, Kozlow JH, Mittal B, Moyer J, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol 2018; 78: 540-559.
https://doi.org/10.1016/j.jaad.2017.10.006 DOI: https://doi.org/10.1016/j.jaad.2017.10.006
Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med 2005; 353: 2262-2269.
https://doi.org/10.1056/NEJMra044151 DOI: https://doi.org/10.1056/NEJMra044151
Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature 2001; 411: 349-354.
https://doi.org/10.1038/35077219 DOI: https://doi.org/10.1038/35077219
Scales SJ, de Sauvage FJ. Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci 2009; 30: 303-312.
https://doi.org/10.1016/j.tips.2009.03.007 DOI: https://doi.org/10.1016/j.tips.2009.03.007
McMillan R, Matsui W. Molecular pathways: the hedgehog signaling pathway in cancer. Clin Cancer Res 2012; 18: 4883-4888.
https://doi.org/10.1158/1078-0432.CCR-11-2509 DOI: https://doi.org/10.1158/1078-0432.CCR-11-2509
Abe Y, Tanaka N. Roles of the hedgehog signaling pathway in epidermal and hair follicle development, homeostasis, and cancer. J Dev Biol 2017; 5: 12.
https://doi.org/10.3390/jdb5040012 DOI: https://doi.org/10.3390/jdb5040012
Summary of product characteristics. https://www.ema.europa.eu/en/medicines/human/EPAR/odomzo#product-information-section.
Migden MR, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, 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: 716-728.
https://doi.org/10.1016/S1470-2045(15)70100-2 DOI: https://doi.org/10.1016/S1470-2045(15)70100-2
Lear JT, Migden MR, Lewis KD, Chang ALS, Guminski A, Gutzmer R, et al. Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol 2018; 32: 372-381.
https://doi.org/10.1111/jdv.14542 DOI: https://doi.org/10.1111/jdv.14542
Gutzmer R, Robert C, Loquai C, Schadendorf D, Squittieri N, Arntz R et al. Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis. BMC Cancer 2021; 21: 1244.
https://doi.org/10.1186/s12885-021-08968-1 DOI: https://doi.org/10.1186/s12885-021-08968-1
Dummer R, Guminksi A, Gutzmer R, Lear JT, Lewis KD, Chang ALS, et al. Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study. Br J Dermatol 2020; 182: 1369-1378.
https://doi.org/10.1111/bjd.18552 DOI: https://doi.org/10.1111/bjd.18552
Sekulic A, Migden MR, Basset-Seguin N, Garbe C, Gesierich A, Lao CD, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer 2017; 17: 332.
https://doi.org/10.1186/s12885-017-3286-5 DOI: https://doi.org/10.1186/s12885-017-3286-5
Villani A, Fabbrocini G, Costa C, Scalvenzi M. Complete remission of an advanced basal cell carcinoma after only 3-month treatment with sonidegib: report of a case and drug management during COVID-19 pandemic. Dermatol Ther 2020; 33: e14200.
https://doi.org/10.1111/dth.14200 DOI: https://doi.org/10.1111/dth.14200
Wang K, Patel M, Prabhu AV, Lewis GD. First reported case of concurrent sonidegib and radiotherapy for recurrent, advanced basal cell carcinoma. Rep Pract Oncol Radiother 2021; 26: 149-152.
https://doi.org/10.5603/RPOR.a2021.0010 DOI: https://doi.org/10.5603/RPOR.a2021.0010
Villani A, Costa C, Fabbrocini G, Scalvenzi M. Systemic hedgehog inhibitors to treat locally advanced basal cell carcinomas of the head-neck region: a retrospective study. Dermatol Ther 2021: e15036.
https://doi.org/10.1111/dth.15036 DOI: https://doi.org/10.1111/dth.15036
Dummer R, Guminski A, Gutzmer R, Dirix L, Lewis KD, Combemale P, et al. The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): a phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol 2016; 75: 113-125.e5.
https://doi.org/10.1016/j.jaad.2016.02.1226 DOI: https://doi.org/10.1016/j.jaad.2016.02.1226
Erivedge - Summary of product characteristics. https://www.ema.europa.eu/en/medicines/human/EPAR/erivedge#product-information-section.
Lacouture ME, Dreno B, Ascierto PA, Dummer R, Basset-Seguin N, Fife K, et al. Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma. Oncologist 2016; 21: 1218-1229.
https://doi.org/10.1634/theoncologist.2016-0186 DOI: https://doi.org/10.1634/theoncologist.2016-0186
Romero D. Cemiplimab is a new option in BCC. Nat Rev Clin Oncol 2021; 18: 400.
https://doi.org/10.1038/s41571-021-00528-7 DOI: https://doi.org/10.1038/s41571-021-00528-7
Herms F, Lambert J, Grob JJ, Haudebourg L, Bagot M, Dalac S, et al. Follow-up of patients with complete remission of locally advanced basal cell carcinoma after vismodegib discontinuation: a multicenter French study of 116 patients. J Clin Oncol 2019; 37: 3275-3282.
https://doi.org/10.1200/JCO.18.00794 DOI: https://doi.org/10.1200/JCO.18.00794
Bassompierre A, Dalac S, Dreno B, Neidhardt EM, Maubec E, Capelle C et al. Efficacy of sonic hedgehog inhibitors rechallenge, after initial complete response in recurrent advanced basal cell carcinoma: a retrospective study from the CARADERM database. ESMO Open 2021; 6: 100284.
https://doi.org/10.1016/j.esmoop.2021.100284 DOI: https://doi.org/10.1016/j.esmoop.2021.100284
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