*Result*: Safety and Efficacy of Vismodegib and Sonidegib in Advanced Basal Cell Carcinoma of the Head and Neck: A Systematic Review and Meta-Analysis.
Title:
Safety and Efficacy of Vismodegib and Sonidegib in Advanced Basal Cell Carcinoma of the Head and Neck: A Systematic Review and Meta-Analysis.
Authors:
Doyle CM; Western Health, Footscray Hospital, Footscray, Victoria, Australia.; Plastic and Reconstructive Surgery Unit, The Royal Melbourne Hospital, Parkville, Parkville, Victoria, Australia., Cevik J; Plastic and Reconstructive Surgery Unit, The Royal Melbourne Hospital, Parkville, Parkville, Victoria, Australia., Ramakrishnan A; Plastic and Reconstructive Surgery Unit, The Royal Melbourne Hospital, Parkville, Parkville, Victoria, Australia.; Department of Surgery, the Royal Melbourne Hospital, The University of Melbourne, Parkville, Parkville, Victoria, Australia.
Source:
Head & neck [Head Neck] 2026 Feb; Vol. 48 (2), pp. 504-513. Date of Electronic Publication: 2025 Sep 30.
Publication Type:
Journal Article; Systematic Review; Meta-Analysis
Language:
English
Journal Info:
Publisher: John Wiley And Sons Country of Publication: United States NLM ID: 8902541 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0347 (Electronic) Linking ISSN: 10433074 NLM ISO Abbreviation: Head Neck Subsets: MEDLINE
Imprint Name(s):
Publication: New York, NY : John Wiley And Sons
Original Publication: New York, NY : J. Wiley, c1989-
Original Publication: New York, NY : J. Wiley, c1989-
MeSH Terms:
Basal Cell Carcinoma*/drug therapy , Basal Cell Carcinoma*/pathology , Basal Cell Carcinoma*/mortality , Pyridines*/therapeutic use , Pyridines*/adverse effects , Anilides*/therapeutic use , Anilides*/adverse effects , Head and Neck Neoplasms*/drug therapy , Head and Neck Neoplasms*/pathology , Head and Neck Neoplasms*/mortality , Skin Neoplasms*/drug therapy , Skin Neoplasms*/pathology , Biphenyl Compounds*/therapeutic use , Biphenyl Compounds*/adverse effects , Antineoplastic Agents*/therapeutic use , Antineoplastic Agents*/adverse effects, Humans ; Treatment Outcome
References:
M. C. Cameron, E. Lee, B. P. Hibler, et al., “Basal Cell Carcinoma: Epidemiology; Pathophysiology; Clinical and Histological Subtypes; and Disease Associations,” Journal of the American Academy of Dermatology 80, no. 2 (2019): 303–317, https://doi.org/10.1016/j.jaad.2018.03.060.
A. Bengoa‐González, E. Mencía‐Gutiérrez, M. Garrido, E. Salvador, and M. D. Lago‐Llinás, “Advanced Periocular Basal Cell Carcinoma With Orbital Invasion: Update on Management and Treatment Advances,” Journal of Ophthalmology 2024 (2024): 4347707, https://doi.org/10.1155/2024/4347707.
A. K. Ganti and A. Kessinger, “Systemic Therapy for Disseminated Basal Cell Carcinoma: An Uncommon Manifestation of a Common Cancer,” Cancer Treatment Reviews 37, no. 6 (2011): 440–443, https://doi.org/10.1016/j.ctrv.2010.12.002.
N. Gupta and E. S. Ruiz, “Current Perspectives in the Treatment of Locally Advanced Basal Cell Carcinoma,” Drug Design, Development and Therapy 16 (2022): 183–190, https://doi.org/10.2147/dddt.S325852.
M. McCusker, N. Basset‐Seguin, R. Dummer, et al., “Metastatic Basal Cell Carcinoma: Prognosis Dependent on Anatomic Site and Spread of Disease,” European Journal of Cancer 50, no. 4 (2014): 774–783, https://doi.org/10.1016/j.ejca.2013.12.013.
K. Tanese, “Diagnosis and Management of Basal Cell Carcinoma,” Current Treatment Options in Oncology 20, no. 2 (2019): 13, https://doi.org/10.1007/s11864‐019‐0610‐0.
A. Wysong, S. Z. Aasi, and J. Y. Tang, “Update on Metastatic Basal Cell Carcinoma: A Summary of Published Cases From 1981 Through 2011,” JAMA Dermatology 149, no. 5 (2013): 615–616, https://doi.org/10.1001/jamadermatol.2013.3064.
A. M. Skoda, D. Simovic, V. Karin, V. Kardum, S. Vranic, and L. Serman, “The Role of the Hedgehog Signaling Pathway in Cancer: A Comprehensive Review,” Bosnian Journal of Basic Medical Sciences 18, no. 1 (2018): 8–20, https://doi.org/10.17305/bjbms.2018.2756.
L. Feller, R. A. G. Khammissa, B. Kramer, M. Altini, and J. Lemmer, “Basal Cell Carcinoma, Squamous Cell Carcinoma and Melanoma of the Head and Face,” Head & Face Medicine 12 (2016): 11, https://doi.org/10.1186/s13005‐016‐0106‐0.
E. Leavitt, G. Lask, and S. Martin, “Sonic Hedgehog Pathway Inhibition in the Treatment of Advanced Basal Cell Carcinoma,” Current Treatment Options in Oncology 20, no. 11 (2019): 84, https://doi.org/10.1007/s11864‐019‐0683‐9.
A. Sekulic, M. R. Migden, A. E. Oro, et al., “Efficacy and Safety of Vismodegib in Advanced Basal‐Cell Carcinoma,” New England Journal of Medicine 366, no. 23 (2012): 2171–2179, https://doi.org/10.1056/NEJMoa1113713.
A. Nguyen, P. Xie, I. V. Litvinov, and P. Lefrançois, “Efficacy and Safety of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: An Updated Systematic Review and Meta‐Analysis (2009‐2022),” American Journal of Clinical Dermatology 24, no. 3 (2023): 359–374, https://doi.org/10.1007/s40257‐023‐00763‐x.
A. L. S. Chang, D. C. Tran, J. G. D. Cannon, et al., “Pembrolizumab for Advanced Basal Cell Carcinoma: An Investigator‐Initiated, Proof‐Of‐Concept Study,” Journal of the American Academy of Dermatology 80, no. 2 (2019): 564–566, https://doi.org/10.1016/j.jaad.2018.08.017.
K. Peris, M. C. Fargnoli, R. Kaufmann, et al., “European Consensus‐Based Interdisciplinary Guideline for Diagnosis and Treatment of Basal Cell Carcinoma‐Update 2023,” European Journal of Cancer 192 (2023): 113254, https://doi.org/10.1016/j.ejca.2023.113254.
M. Ben Ishai, A. Tiosano, E. Fenig, G. Ben Simon, and I. Yassur, “Outcomes of Vismodegib for Periocular Locally Advanced Basal Cell Carcinoma From an Open‐Label Trial,” JAMA Ophthalmology 138, no. 7 (2020): 749–755, https://doi.org/10.1001/jamaophthalmol.2020.1539.
M. J. Page, J. E. McKenzie, P. M. Bossuyt, et al., “The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews,” BMJ (Clinical Research Ed.) 372 (2021): n71, https://doi.org/10.1136/bmj.n71.
N. Bertrand, P. Guerreschi, N. Basset‐Seguin, et al., “Vismodegib in Neoadjuvant Treatment of Locally Advanced Basal Cell Carcinoma: First Results of a Multicenter, Open‐Label, Phase 2 Trial (VISMONEO Study): Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma,” EClinicalMedicine 35 (2021): 100844, https://doi.org/10.1016/j.eclinm.2021.100844.
H. Cinkir, Ö. Sever, and F. Teker, “Vismodegib for Patients With Advanced Basal Cell Carcinoma: One Center's Experience,” Journal of Oncological Sciences 6 (2020): 5–9, https://doi.org/10.37047/jos.2019‐71992.
D. S. Curragh, S. C. Huilgol, and D. Selva, “Neoadjuvant Vismodegib in the Management of Locally Advanced Periocular Basal Cell Carcinoma,” Eye (London, England) 35, no. 10 (2021): 2740–2745, https://doi.org/10.1038/s41433‐020‐01291‐2.
V. De Giorgi, L. Trane, G. Pieretti, et al., “Treatment of Periocular Advanced Basal Cell Carcinoma With Hedgehog Pathway Inhibitors: A Single‐Center Study and a New Dedicated Therapeutic Protocol,” Dermatology Reports 13, no. 3 (2021): 9240, https://doi.org/10.4081/dr.2021.9240.
H. Demirci, F. Worden, C. C. Nelson, V. M. Elner, and A. Kahana, “Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area,” Ophthalmic Plastic and Reconstructive Surgery 31, no. 6 (2015): 463–466, https://doi.org/10.1097/iop.0000000000000388.
H. S. Gill, E. E. Moscato, A. L. Chang, S. Soon, and R. Z. Silkiss, “Vismodegib for Periocular and Orbital Basal Cell Carcinoma,” JAMA Ophthalmology 131, no. 12 (2013): 1591–1594, https://doi.org/10.1001/jamaophthalmol.2013.5018.
A. Kahana, S. P. Unsworth, C. A. Andrews, et al., “Vismodegib for Preservation of Visual Function in Patients With Advanced Periocular Basal Cell Carcinoma: The VISORB Trial,” Oncologist 26, no. 7 (2021): e1240–e1249, https://doi.org/10.1002/onco.13820.
H. Oliphant, J. Laybourne, K. Chan, et al., “Vismodegib for Periocular Basal Cell Carcinoma: An International Multicentre Case Series,” Eye (London, England) 34, no. 11 (2020): 2076–2081, https://doi.org/10.1038/s41433‐020‐0778‐3.
R. Ruiz‐Villaverde, E. Herrera‐Acosta, A. Ruiz de Casas, et al., “Multicenter Retrospective Andalusian Study of the Use of Sonidegib for the Treatment of Local Advanced Basal Cell Carcinoma in Real Clinical Practice,” Journal of Clinical Medicine 12, no. 17 (2023): 5631, https://doi.org/10.3390/jcm12175631.
O. Sagiv, P. Nagarajan, R. Ferrarotto, et al., “Ocular Preservation With Neoadjuvant Vismodegib in Patients With Locally Advanced Periocular Basal Cell Carcinoma,” British Journal of Ophthalmology 103, no. 6 (2019): 775–780, https://doi.org/10.1136/bjophthalmol‐2018‐312277.
G. Tauber, L. Pavlovsky, E. Fenig, and E. Hodak, “Vismodegib for Radiation‐Induced Multiple Basal Cell Carcinomas (BCCs) of the Scalp,” Journal of the American Academy of Dermatology 73, no. 5 (2015): 799–801, https://doi.org/10.1016/j.jaad.2015.07.016.
A. Villani, C. Costa, G. Fabbrocini, and M. Scalvenzi, “Systemic Hedgehog Inhibitors to Treat Locally Advanced Basal Cell Carcinomas of the Head‐Neck Region: A Retrospective Study,” Dermatologic Therapy 34, no. 5 (2021): e15036, https://doi.org/10.1111/dth.15036.
A. Villani, G. Fabbrocini, G. Micali, L. Fornaro, L. Potestio, and M. Scalvenzi, “The Efficacy of Sonidegib in Treating Locally Advanced Basal Cell Carcinoma Involving the Periocular Area,” Dermatology and Therapy 13, no. 9 (2023): 2121–2126, https://doi.org/10.1007/s13555‐023‐00985‐1.
K. Y. Wong, K. Fife, J. T. Lear, R. D. Price, and A. J. Durrani, “Vismodegib for Locally Advanced Periocular and Orbital Basal Cell Carcinoma: A Review of 15 Consecutive Cases,” Plastic and Reconstructive Surgery – Global Open 5, no. 7 (2017): e1424, https://doi.org/10.1097/gox.0000000000001424.
C. Xavier, E. Lopes, C. Bexiga, C. Moura, E. Gouveia, and A. F. Duarte, “Vismodegib for Treatment of Periocular Basal Cell Carcinoma – 6‐Year Experience From a Tertiary Cancer Center,” Anais Brasileiros de Dermatologia 96, no. 6 (2021): 712–716, https://doi.org/10.1016/j.abd.2021.04.012.
O. K. Ozgur, V. Yin, E. Chou, et al., “Hedgehog Pathway Inhibition for Locally Advanced Periocular Basal Cell Carcinoma and Basal Cell Nevus Syndrome,” American Journal of Ophthalmology 160, no. 2 (2015): 220–227.e2, https://doi.org/10.1016/j.ajo.2015.04.040.
A. J. Stratigos, A. Sekulic, K. Peris, et al., “Cemiplimab in Locally Advanced Basal Cell Carcinoma After Hedgehog Inhibitor Therapy: An Open‐Label, Multi‐Centre, Single‐Arm, Phase 2 Trial,” Lancet Oncology 22, no. 6 (2021): 848–857, https://doi.org/10.1016/s1470‐2045(21)00126‐1.
A. A. Jacobsen, A. S. Aldahan, O. B. Hughes, V. V. Shah, and J. Strasswimmer, “Hedgehog Pathway Inhibitor Therapy for Locally Advanced and Metastatic Basal Cell Carcinoma: A Systematic Review and Pooled Analysis of Interventional Studies,” JAMA Dermatology 152, no. 7 (2016): 816–824, https://doi.org/10.1001/jamadermatol.2016.0780.
R. C. Gerring, C. T. Ott, J. M. Curry, Z. B. Sargi, and S. T. Wester, “Orbital Exenteration for Advanced Periorbital Non‐Melanoma Skin Cancer: Prognostic Factors and Survival,” Eye (London, England) 31, no. 3 (2017): 379–388, https://doi.org/10.1038/eye.2016.218.
P. Xie and P. Lefrançois, “Efficacy, Safety, and Comparison of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: A Systematic Review and Meta‐Analysis,” Journal of the American Academy of Dermatology 79, no. 6 (2018): 1089–1100.e17, https://doi.org/10.1016/j.jaad.2018.07.004.
M. E. Lacouture, B. Dréno, P. A. Ascierto, et al., “Characterization and Management of Hedgehog Pathway Inhibitor‐Related Adverse Events in Patients With Advanced Basal Cell Carcinoma,” Oncologist 21, no. 10 (2016): 1218–1229, https://doi.org/10.1634/theoncologist.2016‐0186.
S. V. Mohan, J. Chang, S. Li, A. S. Henry, D. J. Wood, and A. L. Chang, “Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma,” JAMA Dermatology 152, no. 5 (2016): 527–532, https://doi.org/10.1001/jamadermatol.2015.4330.
A. Bengoa‐González, E. Mencía‐Gutiérrez, M. Garrido, E. Salvador, and M. D. Lago‐Llinás, “Advanced Periocular Basal Cell Carcinoma With Orbital Invasion: Update on Management and Treatment Advances,” Journal of Ophthalmology 2024 (2024): 4347707, https://doi.org/10.1155/2024/4347707.
A. K. Ganti and A. Kessinger, “Systemic Therapy for Disseminated Basal Cell Carcinoma: An Uncommon Manifestation of a Common Cancer,” Cancer Treatment Reviews 37, no. 6 (2011): 440–443, https://doi.org/10.1016/j.ctrv.2010.12.002.
N. Gupta and E. S. Ruiz, “Current Perspectives in the Treatment of Locally Advanced Basal Cell Carcinoma,” Drug Design, Development and Therapy 16 (2022): 183–190, https://doi.org/10.2147/dddt.S325852.
M. McCusker, N. Basset‐Seguin, R. Dummer, et al., “Metastatic Basal Cell Carcinoma: Prognosis Dependent on Anatomic Site and Spread of Disease,” European Journal of Cancer 50, no. 4 (2014): 774–783, https://doi.org/10.1016/j.ejca.2013.12.013.
K. Tanese, “Diagnosis and Management of Basal Cell Carcinoma,” Current Treatment Options in Oncology 20, no. 2 (2019): 13, https://doi.org/10.1007/s11864‐019‐0610‐0.
A. Wysong, S. Z. Aasi, and J. Y. Tang, “Update on Metastatic Basal Cell Carcinoma: A Summary of Published Cases From 1981 Through 2011,” JAMA Dermatology 149, no. 5 (2013): 615–616, https://doi.org/10.1001/jamadermatol.2013.3064.
A. M. Skoda, D. Simovic, V. Karin, V. Kardum, S. Vranic, and L. Serman, “The Role of the Hedgehog Signaling Pathway in Cancer: A Comprehensive Review,” Bosnian Journal of Basic Medical Sciences 18, no. 1 (2018): 8–20, https://doi.org/10.17305/bjbms.2018.2756.
L. Feller, R. A. G. Khammissa, B. Kramer, M. Altini, and J. Lemmer, “Basal Cell Carcinoma, Squamous Cell Carcinoma and Melanoma of the Head and Face,” Head & Face Medicine 12 (2016): 11, https://doi.org/10.1186/s13005‐016‐0106‐0.
E. Leavitt, G. Lask, and S. Martin, “Sonic Hedgehog Pathway Inhibition in the Treatment of Advanced Basal Cell Carcinoma,” Current Treatment Options in Oncology 20, no. 11 (2019): 84, https://doi.org/10.1007/s11864‐019‐0683‐9.
A. Sekulic, M. R. Migden, A. E. Oro, et al., “Efficacy and Safety of Vismodegib in Advanced Basal‐Cell Carcinoma,” New England Journal of Medicine 366, no. 23 (2012): 2171–2179, https://doi.org/10.1056/NEJMoa1113713.
A. Nguyen, P. Xie, I. V. Litvinov, and P. Lefrançois, “Efficacy and Safety of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: An Updated Systematic Review and Meta‐Analysis (2009‐2022),” American Journal of Clinical Dermatology 24, no. 3 (2023): 359–374, https://doi.org/10.1007/s40257‐023‐00763‐x.
A. L. S. Chang, D. C. Tran, J. G. D. Cannon, et al., “Pembrolizumab for Advanced Basal Cell Carcinoma: An Investigator‐Initiated, Proof‐Of‐Concept Study,” Journal of the American Academy of Dermatology 80, no. 2 (2019): 564–566, https://doi.org/10.1016/j.jaad.2018.08.017.
K. Peris, M. C. Fargnoli, R. Kaufmann, et al., “European Consensus‐Based Interdisciplinary Guideline for Diagnosis and Treatment of Basal Cell Carcinoma‐Update 2023,” European Journal of Cancer 192 (2023): 113254, https://doi.org/10.1016/j.ejca.2023.113254.
M. Ben Ishai, A. Tiosano, E. Fenig, G. Ben Simon, and I. Yassur, “Outcomes of Vismodegib for Periocular Locally Advanced Basal Cell Carcinoma From an Open‐Label Trial,” JAMA Ophthalmology 138, no. 7 (2020): 749–755, https://doi.org/10.1001/jamaophthalmol.2020.1539.
M. J. Page, J. E. McKenzie, P. M. Bossuyt, et al., “The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews,” BMJ (Clinical Research Ed.) 372 (2021): n71, https://doi.org/10.1136/bmj.n71.
N. Bertrand, P. Guerreschi, N. Basset‐Seguin, et al., “Vismodegib in Neoadjuvant Treatment of Locally Advanced Basal Cell Carcinoma: First Results of a Multicenter, Open‐Label, Phase 2 Trial (VISMONEO Study): Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma,” EClinicalMedicine 35 (2021): 100844, https://doi.org/10.1016/j.eclinm.2021.100844.
H. Cinkir, Ö. Sever, and F. Teker, “Vismodegib for Patients With Advanced Basal Cell Carcinoma: One Center's Experience,” Journal of Oncological Sciences 6 (2020): 5–9, https://doi.org/10.37047/jos.2019‐71992.
D. S. Curragh, S. C. Huilgol, and D. Selva, “Neoadjuvant Vismodegib in the Management of Locally Advanced Periocular Basal Cell Carcinoma,” Eye (London, England) 35, no. 10 (2021): 2740–2745, https://doi.org/10.1038/s41433‐020‐01291‐2.
V. De Giorgi, L. Trane, G. Pieretti, et al., “Treatment of Periocular Advanced Basal Cell Carcinoma With Hedgehog Pathway Inhibitors: A Single‐Center Study and a New Dedicated Therapeutic Protocol,” Dermatology Reports 13, no. 3 (2021): 9240, https://doi.org/10.4081/dr.2021.9240.
H. Demirci, F. Worden, C. C. Nelson, V. M. Elner, and A. Kahana, “Efficacy of Vismodegib (Erivedge) for Basal Cell Carcinoma Involving the Orbit and Periocular Area,” Ophthalmic Plastic and Reconstructive Surgery 31, no. 6 (2015): 463–466, https://doi.org/10.1097/iop.0000000000000388.
H. S. Gill, E. E. Moscato, A. L. Chang, S. Soon, and R. Z. Silkiss, “Vismodegib for Periocular and Orbital Basal Cell Carcinoma,” JAMA Ophthalmology 131, no. 12 (2013): 1591–1594, https://doi.org/10.1001/jamaophthalmol.2013.5018.
A. Kahana, S. P. Unsworth, C. A. Andrews, et al., “Vismodegib for Preservation of Visual Function in Patients With Advanced Periocular Basal Cell Carcinoma: The VISORB Trial,” Oncologist 26, no. 7 (2021): e1240–e1249, https://doi.org/10.1002/onco.13820.
H. Oliphant, J. Laybourne, K. Chan, et al., “Vismodegib for Periocular Basal Cell Carcinoma: An International Multicentre Case Series,” Eye (London, England) 34, no. 11 (2020): 2076–2081, https://doi.org/10.1038/s41433‐020‐0778‐3.
R. Ruiz‐Villaverde, E. Herrera‐Acosta, A. Ruiz de Casas, et al., “Multicenter Retrospective Andalusian Study of the Use of Sonidegib for the Treatment of Local Advanced Basal Cell Carcinoma in Real Clinical Practice,” Journal of Clinical Medicine 12, no. 17 (2023): 5631, https://doi.org/10.3390/jcm12175631.
O. Sagiv, P. Nagarajan, R. Ferrarotto, et al., “Ocular Preservation With Neoadjuvant Vismodegib in Patients With Locally Advanced Periocular Basal Cell Carcinoma,” British Journal of Ophthalmology 103, no. 6 (2019): 775–780, https://doi.org/10.1136/bjophthalmol‐2018‐312277.
G. Tauber, L. Pavlovsky, E. Fenig, and E. Hodak, “Vismodegib for Radiation‐Induced Multiple Basal Cell Carcinomas (BCCs) of the Scalp,” Journal of the American Academy of Dermatology 73, no. 5 (2015): 799–801, https://doi.org/10.1016/j.jaad.2015.07.016.
A. Villani, C. Costa, G. Fabbrocini, and M. Scalvenzi, “Systemic Hedgehog Inhibitors to Treat Locally Advanced Basal Cell Carcinomas of the Head‐Neck Region: A Retrospective Study,” Dermatologic Therapy 34, no. 5 (2021): e15036, https://doi.org/10.1111/dth.15036.
A. Villani, G. Fabbrocini, G. Micali, L. Fornaro, L. Potestio, and M. Scalvenzi, “The Efficacy of Sonidegib in Treating Locally Advanced Basal Cell Carcinoma Involving the Periocular Area,” Dermatology and Therapy 13, no. 9 (2023): 2121–2126, https://doi.org/10.1007/s13555‐023‐00985‐1.
K. Y. Wong, K. Fife, J. T. Lear, R. D. Price, and A. J. Durrani, “Vismodegib for Locally Advanced Periocular and Orbital Basal Cell Carcinoma: A Review of 15 Consecutive Cases,” Plastic and Reconstructive Surgery – Global Open 5, no. 7 (2017): e1424, https://doi.org/10.1097/gox.0000000000001424.
C. Xavier, E. Lopes, C. Bexiga, C. Moura, E. Gouveia, and A. F. Duarte, “Vismodegib for Treatment of Periocular Basal Cell Carcinoma – 6‐Year Experience From a Tertiary Cancer Center,” Anais Brasileiros de Dermatologia 96, no. 6 (2021): 712–716, https://doi.org/10.1016/j.abd.2021.04.012.
O. K. Ozgur, V. Yin, E. Chou, et al., “Hedgehog Pathway Inhibition for Locally Advanced Periocular Basal Cell Carcinoma and Basal Cell Nevus Syndrome,” American Journal of Ophthalmology 160, no. 2 (2015): 220–227.e2, https://doi.org/10.1016/j.ajo.2015.04.040.
A. J. Stratigos, A. Sekulic, K. Peris, et al., “Cemiplimab in Locally Advanced Basal Cell Carcinoma After Hedgehog Inhibitor Therapy: An Open‐Label, Multi‐Centre, Single‐Arm, Phase 2 Trial,” Lancet Oncology 22, no. 6 (2021): 848–857, https://doi.org/10.1016/s1470‐2045(21)00126‐1.
A. A. Jacobsen, A. S. Aldahan, O. B. Hughes, V. V. Shah, and J. Strasswimmer, “Hedgehog Pathway Inhibitor Therapy for Locally Advanced and Metastatic Basal Cell Carcinoma: A Systematic Review and Pooled Analysis of Interventional Studies,” JAMA Dermatology 152, no. 7 (2016): 816–824, https://doi.org/10.1001/jamadermatol.2016.0780.
R. C. Gerring, C. T. Ott, J. M. Curry, Z. B. Sargi, and S. T. Wester, “Orbital Exenteration for Advanced Periorbital Non‐Melanoma Skin Cancer: Prognostic Factors and Survival,” Eye (London, England) 31, no. 3 (2017): 379–388, https://doi.org/10.1038/eye.2016.218.
P. Xie and P. Lefrançois, “Efficacy, Safety, and Comparison of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: A Systematic Review and Meta‐Analysis,” Journal of the American Academy of Dermatology 79, no. 6 (2018): 1089–1100.e17, https://doi.org/10.1016/j.jaad.2018.07.004.
M. E. Lacouture, B. Dréno, P. A. Ascierto, et al., “Characterization and Management of Hedgehog Pathway Inhibitor‐Related Adverse Events in Patients With Advanced Basal Cell Carcinoma,” Oncologist 21, no. 10 (2016): 1218–1229, https://doi.org/10.1634/theoncologist.2016‐0186.
S. V. Mohan, J. Chang, S. Li, A. S. Henry, D. J. Wood, and A. L. Chang, “Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma,” JAMA Dermatology 152, no. 5 (2016): 527–532, https://doi.org/10.1001/jamadermatol.2015.4330.
Contributed Indexing:
Keywords: adult; basal cell carcinoma; head and neck cancer; hedgehog pathway inhibitors; hedgehog proteins; humans; immunotherapy; sonidegib; vismodegib
Substance Nomenclature:
0 (Pyridines)
0 (Anilides)
0 (HhAntag691)
0RLU3VTK5M (sonidegib)
0 (Biphenyl Compounds)
0 (Antineoplastic Agents)
0 (Anilides)
0 (HhAntag691)
0RLU3VTK5M (sonidegib)
0 (Biphenyl Compounds)
0 (Antineoplastic Agents)
Entry Date(s):
Date Created: 20250930 Date Completed: 20260113 Latest Revision: 20260127
Update Code:
20260130
DOI:
10.1002/hed.70056
PMID:
41025405
Database:
MEDLINE
*Further Information*
*Importance: Basal cell carcinoma (BCC) is the most prevalent malignancy globally, with 75% occurring in the head and neck. Hedgehog pathway inhibitors (HHIs) may provide a treatment for locally advanced BCC (laBCC) and metastatic BCC (mBCC) of the head and neck.
Objective: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of these treatments specifically in the head and neck region.
Data Sources: An electronic database search was conducted in June 2024 across Embase, MEDLINE, CINAHL, and ClinicalTrials.gov. There were no date limits applied, with search constraints consisting of the English language.
Study Selection: Included were studies involving adults with confirmed laBCC or mBCC of the head and neck treated with either vismodegib or sonidegib, with histological or radiological confirmation. Studies were excluded if they involved concurrent treatments or lacked quantitative measures. After full text review was completed, there were 17 studies for inclusion.
Data Extraction and Synthesis: This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines using two independent observers. Data extraction was performed using a standardized Microsoft Excel Form. Statistical analyses were conducted using meta-analysis software on jamovi using a random effects model.
Main Outcome(s) and Measure(s): This study initially aimed to investigate both systemic immunotherapies and targeted therapies, but no articles were identified for systemic immunotherapies for laBCC or mBCC of the head and neck region. Thus, the sole focus of this article became targeted therapies. Primary outcomes assessed were overall response rate (ORR), complete response (CR), and partial response (PR), alongside the prevalence of adverse effects.
Findings: Seventeen studies involving 522 patients were analyzed, revealing a pooled ORR of 84.2% (95% CI: 77.1-91.3), CR of 33.8%, and PR of 47.7%. Common adverse effects included muscle spasms, dysgeusia, and fatigue, with a discontinuation rate of 13.2% due to adverse events.
Conclusions and Relevance: This systematic review and meta-analysis demonstrated a high efficacy of vismodegib and sonidegib for treating advanced BCCs in the head and neck region, suggesting a viable option when surgery is not feasible. Further high-quality research is necessary to optimize treatment outcomes for this patient population.
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