Tirbanibulin as a Novel Treatment in Actinic Keratosis: A Literature Review
DOI:
https://doi.org/10.12775/JEHS.2024.70.55328Keywords
actinic keratosis, actinic keratosis treatment, tirbanibulinAbstract
Introduction and purpose: Actinic keratosis (AK) is a common dermatological condition that primarily affects fair-skinned individuals due to cumulative ultraviolet light exposure, potentially leading to squamous cell carcinoma (SCC). AK therapy is divided into two main branches: lesion-directed therapy (cryotherapy, lasers, and surgical methods) and field cancerization-directed therapy (photodynamic therapy and topical agents). Unfortunately, the occurrence of local skin reactions (LSRs) and the therapy duration counted in weeks disrupt patient compliance. This study aims to review the clinical trials concerning the efficacy, safety, and adverse effects of tirbanibulin, a novel promising treatment for AK, which led to its approval and therapeutic development.
Materials and methods: Literature available in PubMed and GoogleScholar databases were reviewed using the following keywords: actinic keratosis; actinic keratosis treatment; tirbanibulin.
Results: Tirbanibulin's mechanism involves inducing apoptosis by inhibiting microtubule polymerization, which distinguishes it from other treatments that often cause significant inflammation. Clinical trials demonstrate its high efficacy in clearing AK lesions with a favorable safety profile, leading to regulatory approval. The ease of use and short therapy duration (5 days) ensure patient compliance and satisfaction with the treatment.
Conclusion: Further longitudinal studies are necessary to confirm the long-term benefits and positioning of tirbanibulin in AK therapy. Raising public awareness about AK and the importance of early treatment with effective options like tirbanibulin is crucial for improving public health outcomes.
References
Blauvelt A, Kempers S, Lain E, et al. Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis. N Engl J Med. 2021;384(6):512-520. doi:10.1056/NEJMoa2024040
Thamm JR, Welzel J, Schuh S. Diagnosis and therapy of actinic keratosis. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2024;22(5):675-690. doi:10.1111/ddg.15288
Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol. 2019;94(6):637-657. doi:10.1016/j.abd.2019.10.004
Dianzani C, Conforti C, Giuffrida R, et al. Current therapies for actinic keratosis. Int J Dermatol. 2020;59(6):677-684. doi:10.1111/ijd.14767
Salmon N, Tidman MJ. Managing actinic keratosis in primary care. Practitioner. 2016;260(1797):25-29.
Siegel JA, Korgavkar K, Weinstock MA. Current perspective on actinic keratosis: a review. Br J Dermatol. 2017;177(2):350-358. doi:10.1111/bjd.14852
de Oliveira ECV, da Motta VRV, Pantoja PC, et al. Actinic keratosis - review for clinical practice. Int J Dermatol. 2019;58(4):400-407. doi:10.1111/ijd.14147
Dao DPD, Sahni VN, Sahni DR, Balogh EA, Grada A, Feldman SR. 1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses. Ann Pharmacother. 2022;56(4):494-500. doi:10.1177/10600280211031329
Miller AC, Adjei S, Temiz LA, Tyring SK. Tirbanibulin for the Treatment of Actinic Keratosis: A Review. Skin Therapy Lett. 2022;27(4):4-7.
Röwert-Huber J, Patel MJ, Forschner T, et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification. Br J Dermatol. 2007;156 Suppl 3:8-12. doi:10.1111/j.1365-2133.2007.07860.x
Li Y, Wang J, Xiao W, Liu J, Zha X. Risk Factors for Actinic Keratoses: A Systematic Review and Meta-Analysis. Indian J Dermatol. 2022;67(1):92. doi:10.4103/ijd.ijd_859_21
Balcere A, Rone Kupfere M, Čēma I, Krūmiņa A. Prevalence, Discontinuation Rate, and Risk Factors for Severe Local Site Reactions with Topical Field Treatment Options for Actinic Keratosis of the Face and Scalp. Medicina (Kaunas). 2019;55(4):92. doi:10.3390/medicina55040092
GUORGIS G, ANDERSON CD, LYTH J, FALK M. Actinic Keratosis Diagnosis and Increased Risk of Developing Skin Cancer: A 10-year Cohort Study of 17,651 Patients in Sweden. Acta Derm Venereol. 2020;100(8):5741. doi:10.2340/00015555-3486
Valdés-Morales KL, Peralta-Pedrero ML, Cruz FJS, Morales-Sánchez MA. Diagnostic Accuracy of Dermoscopy of Actinic Keratosis: A Systematic Review. Dermatol Pract Concept. 2020;10(4):e2020121. doi:10.5826/dpc.1004a121
Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115(11):2523-2530. doi:10.1002/cncr.24284
Dodds A, Chia A, Shumack S. Actinic keratosis: rationale and management. Dermatol Ther (Heidelb). 2014;4(1):11-31. doi:10.1007/s13555-014-0049-y
Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000;42(1 Pt 2):23-24. doi:10.1067/mjd.2000.103339
Schmitz L, Gambichler T, Kost C, et al. Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses. Br J Dermatol. 2019;180(4):916-921. doi:10.1111/bjd.16536
Schmitz L, Kahl P, Majores M, Bierhoff E, Stockfleth E, Dirschka T. Actinic keratosis: correlation between clinical and histological classification systems. J Eur Acad Dermatol Venereol. 2016;30(8):1303-1307. doi:10.1111/jdv.13626
Fernández-Figueras MT, Carrato C, Sáenz X, et al. Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol. 2015;29(5):991-997. doi:10.1111/jdv.12848
Goldenberg G. Treatment considerations in actinic keratosis. J Eur Acad Dermatol Venereol. 2017;31 Suppl 2:12-16. doi:10.1111/jdv.14152
Schlesinger T, Stockfleth E, Grada A, Berman B. Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action. Clin Cosmet Investig Dermatol. 2022;15:2495-2506. doi:10.2147/CCID.S374122
Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021;85(4):e209-e233. doi:10.1016/j.jaad.2021.02.082
Arcuri D, Ramchatesingh B, Lagacé F, et al. Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review. Int J Mol Sci. 2023;24(5):4989. doi:10.3390/ijms24054989
picato-article-20-referral-risks-picato-actinic-keratosis-outweigh-benefits_en.pdf. Accessed July 4, 2024. https://www.ema.europa.eu/en/documents/referral/picato-article-20-referral-risks-picato-actinic-keratosis-outweigh-benefits_en.pdf
Khanna R, Bakshi A, Amir Y, Goldenberg G. Patient satisfaction and reported outcomes on the management of actinic keratosis. Clin Cosmet Investig Dermatol. 2017;10:179-184. doi:10.2147/CCID.S121323
Niu L, Yang J, Yan W, et al. Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1’s low clinical toxicity. Journal of Biological Chemistry. 2019;294(48):18099-18108. doi:10.1074/jbc.RA119.010732
Smolinski MP, Bu Y, Clements J, et al. Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361). J Med Chem. 2018;61(11):4704-4719. doi:10.1021/acs.jmedchem.8b00164
Gilaberte Y, Fernández-Figueras MT. Tirbanibulin: review of its novel mechanism of action and how it fits into the treatment of actinic keratosis. Actas Dermosifiliogr. 2022;113(1):58-66. doi:10.1016/j.ad.2021.07.006
Liu T, Hu W, Dalton HJ, et al. Targeting Src and tubulin in mucinous ovarian carcinoma. Clin Cancer Res. 2013;19(23):10.1158/1078-0432.CCR-13-1305. doi:10.1158/1078-0432.CCR-13-1305
Frame MC. Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta. 2002;1602(2):114-130. doi:10.1016/s0304-419x(02)00040-9
Park SI, Shah AN, Zhang J, Gallick GE. Regulation of angiogenesis and vascular permeability by Src family kinases: opportunities for therapeutic treatment of solid tumors. Expert Opinion on Therapeutic Targets. 2007;11(9):1207-1217. doi:10.1517/14728222.11.9.1207
Ainger SA, Sturm RA. Src and SCC: getting to the FAKs. Exp Dermatol. 2015;24(7):487-488. doi:10.1111/exd.12725
Kim S, Min A, Lee KH, et al. Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis. Cancer Res Treat. 2017;49(3):643-655. doi:10.4143/crt.2016.168
Moore S, Kulkarni V, Moore A, et al. Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells. Arch Dermatol Res. 2024;316(7):455. doi:10.1007/s00403-024-03205-8
Pitzonka L, Cutler M, Bu Y, et al. 465 Tirbanibulin, a novel anti-proliferative and pro-apoptotic agent for the treatment of actinic keratosis. J Invest Dermatol. 2021;141(5):S81. doi:10.1016/j.jid.2021.02.489
Kempers S, DuBois J, Forman S, et al. Tirbanibulin Ointment 1% as a Novel Treatment for Actinic Keratosis: Phase 1 and 2 Results. J Drugs Dermatol. 2020;19(11):1093-1100. doi:10.36849/JDD.2020.5576
Tirbanibulin Ointment 1% as a Novel Treatment for Actinic Keratosis: Phase 1 and 2 Results. JDDonline - Journal of Drugs in Dermatology. Accessed July 4, 2024. https://jddonline.com/articles/tirbanibulin-ointment-1-as-a-novel-treatment-for-actinic-keratosis-phase-1-and-2-results-S1545961620P1093X/
Phase II study of KX2-391 ointment 1%, a novel field treatment for actinic keratosis, based on Src/tubulin polymerization inhibition. Journal of the American Academy of Dermatology. 2018;79(3):AB220. doi:10.1016/j.jaad.2018.05.881
Blauvelt A, Kempers S, Schlesinger T, et al. Tirbanibulin Ointment 1% for Actinic Keratosis (AK): Pooled Data from Two Phase 3 Studies. J of Skin. 2020;4(6):s121-s121. doi:10.25251/skin.4.supp.121
Berman B, Gual A, Grada A, Fumero E, Padulles L, Hernandez F. Efficacy of tirbanibulin ointment 1% across different patient populations: pooled results from two Phase 3 studies. J of Skin. 2022;6(2):s27-s27. doi:10.25251/skin.6.supp.s27
Schlesinger T. Commentary: Impact of Prior Treatment in the Efficacy and Tolerability of Tirbanibulin Ointment 1% for Actinic Keratosis: Pooled Results from Two Phase III Studies. J Clin Aesthet Dermatol. 2022;15(10 Suppl 1):S11-S12.
Dosik J, Cutler DL, Fang J, Padullés L. Contact Sensitization and Phototoxic and Photoallergic Potential of Tirbanibulin 1% Ointment in Healthy Volunteers. JID Innov. 2023;3(2):100170. doi:10.1016/j.xjidi.2022.100170
Schlesinger T, Bhatia N, Berman B, et al. Favorable Safety Profile of Tirbanibulin Ointment 1% for Actinic Keratosis: Pooled Results from Two Phase III Studies. J of Skin. 2020;4(6):s120-s120. doi:10.25251/skin.4.supp.120
Berman B, Schlesinger T, Bhatia N. Complete clearance of actinic keratosis with tirbanibulin ointment 1% is not correlated with the severity of local skin reactions. Poster presentation. 2022. MauiDerm for Dermatologists Maui, Hawaii. Published online January 24, 2022.
Bhatia N. Commentary: Complete Clearance of Actinic Keratosis with Tirbanibulin Ointment 1% is not Correlated with the Severity of Local Skin Reactions. J Clin Aesthet Dermatol. 2022;15(10 Suppl 1):S13-S14.
213189s000lbl.pdf. Accessed July 8, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213189s000lbl.pdf
Eisen DB, Dellavalle RP, Frazer-Green L, Schlesinger TE, Shive M, Wu PA. Focused update: Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2022;87(2):373-374.e5. doi:10.1016/j.jaad.2022.04.013
Dunn A, Han H, Gade A, Berman B. The Area Capable of Being Covered by the Application of 250mg of Tirbanibulin Ointment. J Clin Aesthet Dermatol. 2022;15(3):13-14.
Yavel R, Overcash JS, Cutler D, Fang J, Zhi J. Phase 1 Maximal Use Pharmacokinetic Study of Tirbanibulin Ointment 1% in Subjects With Actinic Keratosis. Clin Pharmacol Drug Dev. 2022;11(3):397-405. doi:10.1002/cpdd.1041
Heppt MV, Dykukha I, Graziadio S, Salido-Vallejo R, Chapman-Rounds M, Edwards M. Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2022;11(6):1654. doi:10.3390/jcm11061654
Dymond A, Green W, Edwards M, Pont MAL, Gupta G. Economic Evaluation of Tirbanibulin for the Treatment of Actinic Keratosis in Scotland. Pharmacoecon Open. 2023;7(3):443-454. doi:10.1007/s41669-023-00410-5
Kirchberger MC, Gfesser M, Erdmann M, Schliep S, Berking C, Heppt MV. Tirbanibulin 1% Ointment Significantly Reduces the Actinic Keratosis Area and Severity Index in Patients with Actinic Keratosis: Results from a Real-World Study. J Clin Med. 2023;12(14):4837. doi:10.3390/jcm12144837
Li Pomi F, Vaccaro M, Pallio G, Rottura M, Irrera N, Borgia F. Tirbanibulin 1% Ointment for Actinic Keratosis: Results from a Real-Life Study. Medicina (Kaunas). 2024;60(2):225. doi:10.3390/medicina60020225
Campione E, Rivieccio A, Gaeta Shumak R, et al. Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses. Pharmaceuticals (Basel). 2023;16(12):1686. doi:10.3390/ph16121686
Mansilla-Polo M, Abril-Pérez C, Martín-Torregrosa D, et al. Effectiveness, safety and satisfaction of 1% tirbanibulin ointment in the treatment of actinic keratoses: A prospective study in real clinical practice. Australasian Journal of Dermatology. 2023;64(4):560-564. doi:10.1111/ajd.14151
Nazzaro G, Carugno A, Bortoluzzi P, et al. Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real-life Italian multicenter observational study of 250 patients. Int J Dermatol. Published online April 11, 2024. doi:10.1111/ijd.17168
Schlesinger T, Kircik L, Lebwohl M, et al. Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK). J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264
Markham A, Duggan S. Tirbanibulin: First Approval. Drugs. 2021;81(4):509-513. doi:10.1007/s40265-021-01479-0
IGLESIAS-PUZAS Á, CONDE-TABOADA A, CAMPOS-MUÑOZ L, SIRGADO-MARTÍNEZ A, LÓPEZ-BRAN E. 1% Tirbanibulin Ointment for Actinic Keratoses on Upper Extremities: A Retrospective Case Review Study. Acta Derm Venereol. 2023;103:15296. doi:10.2340/actadv.v103.15296
DuBois J, Jones TM, Lee MS, et al. Pharmacokinetics, Safety, and Tolerability of a Single 5-Day Treatment of Tirbanibulin Ointment 1% in 100 cm2 : A Phase 1 Maximal-Use Trial in Patients with Actinic Keratosis. Clin Pharmacol Drug Dev. 2024;13(2):208-218. doi:10.1002/cpdd.1368
Bhatia N, Blauvelt A, Lain E, et al. Safety, Tolerability and Efficacy of Tirbanibulin Ointment 1% Treatment on 100 cm2 of the Face and Scalp in Patients with Actinic Keratosis: A Phase 3 Study. SKIN The Journal of Cutaneous Medicine. 2023;7:s264. doi:10.25251/skin.7.supp.264
Li Pomi F, Peterle L, d’Aloja A, Di Tano A, Vaccaro M, Borgia F. Anti-aging Effects of Tirbanibulin 1% Ointment: A Real-Life Experience. Dermatol Ther (Heidelb). 2024;14(6):1683-1696. doi:10.1007/s13555-024-01178-0
Hong JB, Wu PY, Qin A, et al. Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results. Pharmaceutics. 2022;14(10):2159. doi:10.3390/pharmaceutics14102159
Blaya Imbernón D, Finello M, Labrandero Hoyos C, et al. Successful treatment of Bowen disease with 1% tirbanibulin ointment. Clin Exp Dermatol. 2023;48(10):1184-1186. doi:10.1093/ced/llad231
Martora F, Ascierto PA, Scalvenzi M, et al. Tirbanibulin ointment to manage recurrence of superficial basal cell carcinoma of the face: case report. Clin Exp Dermatol. 2024;49(2):183-185. doi:10.1093/ced/llad334
Mansilla-Polo M, Abril-Pérez C, Martín-Torregrosa D. Tirbanibulin ointment: A new effective and safe treatment of recalcitrant viral warts. Semergen. 2024;50(8):102278. doi:10.1016/j.semerg.2024.102278
Moore AY, Moore S. Topical tirbanibulin eradication of periungual squamous cell carcinoma. JAAD Case Rep. 2021;14:101-103. doi:10.1016/j.jdcr.2021.06.013
Moore A, Hurley K, Moore SA, Moore L. Real-world experience with histological confirmation of clinical response of squamous cell carcinoma to topical tirbanibulin. JAAD Case Rep. 2023;40:141-144. doi:10.1016/j.jdcr.2023.07.005
Park J, Kang M, Lim A, et al. Synthesis and evaluation of tirbanibulin derivatives: a detailed exploration of the structure-activity relationship for anticancer activity. RSC Adv. 2023;13(50):35583-35591. doi:10.1039/d3ra06790d
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Ilona Sajkiewicz, Nadia Miga-Orczykowska, Paulina Lemieszek, Ilona Jasiuk, Martyna Pustelniak, Justyna Wójtowicz, Katarzyna Krukar, Katarzyna Rudnicka, Ewa Łukaszewska, Klaudia Kister
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 215
Number of citations: 0
