Hedgehog pathway inhibitors for locally advanced and metastatic basal cell carcinoma: A real-world single-center retrospective review

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate. Long-term toxicity includes muscle spasms and weight...

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Published in:	PloS one Vol. 19; no. 4; p. e0297531
Main Authors:	Patel, Shivani, Armbruster, Heather, Pardo, Gretchen, Archambeau, Brianna, Kim, Na Hyun, Jeter, Joanne, Wu, Richard, Kendra, Kari, Contreras, Carlo M, Spaccarelli, Natalie, Dulmage, Brittany, Pootrakul, Llana, Carr, David R, Verschraegen, Claire
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 30-04-2024 Public Library of Science (PLoS)
Subjects:	Adult Aged Aged, 80 and over Anilides - administration & dosage Anilides - therapeutic use Antimitotic agents Antineoplastic agents Basal cell carcinoma Biology and Life Sciences Biphenyl Compounds - therapeutic use Carcinoma, Basal Cell - drug therapy Carcinoma, Basal Cell - pathology Care and treatment Cellular signal transduction Development and progression Dietary supplements Drug therapy Evaluation Female Health aspects Hedgehog Proteins - antagonists & inhibitors Hedgehog Proteins - metabolism Humans Male Medical centers Medical colleges Medicine and Health Sciences Metastasis Middle Aged Neoplasm Metastasis Patient outcomes Prognosis Pyridines - administration & dosage Pyridines - therapeutic use Research and Analysis Methods Retrospective Studies Skin Neoplasms - drug therapy Skin Neoplasms - pathology Social Sciences Ubiquinone - administration & dosage Ubiquinone - analogs & derivatives Ubiquinone - therapeutic use Vismodegib Weight loss United States
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Summary:	Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate. Long-term toxicity includes muscle spasms and weight loss leading to dose decreases. This retrospective chart review also investigates the impact of CoQ10 and calcium supplementation in patients treated with HHI drugs at a single academic medical center from 2012 to 2022. We reviewed the charts of adult patients diagnosed with locally advanced or metastatic BCC treated with vismodegib or sonidegib primarily for progression-free survival (PFS). Secondary objectives included overall survival, BCC-specific survival, time to and reasons for discontinuation, overall response rate, safety and tolerability, use of CoQ10 and calcium supplements, and insurance coverage. Of 55 patients assessable for outcome, 34 (61.8%) had an overall clinical benefit, with 25 (45.4%) having a complete response and 9 (16.3%) a partial response. Stable disease was seen in 14 (25.4%) and 7 (12.7%) progressed. Of the 34 patients who responded to treatment, 9 recurred. Patients who were rechallenged with HHI could respond again. The median overall BCC-specific survival rate at 5 years is 89%. Dose reductions or discontinuations for vismodegib and sonidegib occurred in 59% versus 24% of cases, or 30% versus 9% of cases, respectively. With CoQ10 and calcium supplementation, only 17% required a dose reduction versus 42% without. HHI is highly effective for treating advanced BCC but may require dosing decreases. Sonidegib was better tolerated than vismodegib. CoQ10 and calcium supplementation can effectively prevent muscle spasms.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: Heather Armbruster: Bristol Myers Squibb, Merck Sharp & Dohme, Regeneron
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0297531