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

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Carcinoma, Basal Cell*/drug therapy ; Carcinoma, Basal Cell*/pathology ; Pyridines*/therapeutic use ; Pyridines*/administration & dosage ; Anilides*/therapeutic use ; Anilides*/administration & dosage ; Hedgehog Proteins*/antagonists & inhibitors ; Hedgehog Proteins*/metabolism; Ubiquinone/*analogs & derivatives; Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Skin Neoplasms/drug therapy ; Skin Neoplasms/pathology ; Biphenyl Compounds/therapeutic use ; Adult ; Ubiquinone/therapeutic use ; Ubiquinone/administration & dosage ; Aged, 80 and over ; Neoplasm Metastasis
    • Abstract:
      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.
      Competing Interests: Heather Armbruster: Bristol Myers Squibb, Merck Sharp & Dohme, Regeneron
      (Copyright: © 2024 Patel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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    • Accession Number:
      0 (Pyridines)
      0 (Anilides)
      0 (HhAntag691)
      0 (Hedgehog Proteins)
      0RLU3VTK5M (sonidegib)
      0 (Biphenyl Compounds)
      1339-63-5 (Ubiquinone)
      EJ27X76M46 (coenzyme Q10)
    • Publication Date:
      Date Created: 20240430 Date Completed: 20240430 Latest Revision: 20240502
    • Publication Date:
      20240502
    • Accession Number:
      PMC11060576
    • Accession Number:
      10.1371/journal.pone.0297531
    • Accession Number:
      38687774