Treatment patterns and outcomes for patients with locally advanced basal cell carcinoma before availability of Hedgehog pathway inhibitors: a retrospective chart review

Background: The management of difficult-to-treat periocular basal cell carcinoma becomes very challenging in cases of delayed diagnosis, leading to the development of locally advanced basal cell carcinoma.Objective: The aim of this study was to evaluate the outcomes of Hedgehog pathway inhibitors (vismodegib and sonidegib) treatment in patients affected by periocular locally advanced basal cell carcinoma. We focused on the common adverse events and their correlation with the administration schedule in order to determine a management protocol specific for the periocular area.Methods: This observational prospective study included a single-center case series with patients who were histologically confirmed to have periocular or orbital locally advanced basal cell carcinoma, treated with Hedgehog pathway inhibitors.Results: All patients benefitted in terms of regression or stabilization of the neoplasm. In the first months of treatment, the HPIs were well tolerated, and the first important side effects appeared after about 5 months of continuous use of the drug.Conclusion: These data could lead to a new type of therapeutic scheme where neoadjuvant therapy could be followed by pulse therapy as an adjuvant to surgery.

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High-Risk Recurrence Basal Cell Carcinoma: Focus on Hedgehog Pathway Inhibitors and Review of the Literature

Chemotherapy ◽

10.1159/000509156 ◽

2020 ◽

Vol 65 (1-2) ◽

pp. 2-10 ◽

Cited By ~ 1

Author(s):

Elena Campione ◽

Monia Di Prete ◽

Flavia Lozzi ◽

Caterina Lanna ◽

Giulia Spallone ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Locally Advanced ◽

Indirect Comparison ◽

Molecular Structures ◽

Hedgehog Pathway ◽

European Medicines Agency ◽

Controlled Clinical Trial ◽

Advanced Basal Cell Carcinoma

Basal cell carcinoma is the most common skin tumour, with the majority of the cases occurring on the head and neck district, where cosmetic and functional results are crucial. It can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for most lesions, but aggressive, recurrent, or unresectable tumours can be challenging to manage. Advanced basal cell carcinoma includes high recurrence risk subtypes, in which standard therapies demonstrate lack of efficacy. This led to a need for investigating more deeply the pathogenesis of the disease and to the discovery of the implication of the hedgehog pathway. The development of systemic inhibitors of this pathway provides new treatment options for patients with advanced disease, resulting in survival improvement. Food and Drug Administration, before, and European Medicines Agency later approved 2 Hedgehog pathway inhibitors for the treatment of advanced basal cell carcinomas, vismodegib and sonidegib. Here, we present a review of the current English language literature trying to analyze differences in the 2 drugs as a head-to-head comparison between them has not already been documented in a randomized controlled clinical trial. Although vismodegib and sonidegib showed similar efficacy and safety profiles, in an indirect comparison scenario, sonidegib has shown slightly better outcomes in locally advanced basal cell carcinoma than vismodegib. They present different molecular structures, as they bind different residues on their targets and develop resistance for different mutations. In a future scenario, clinical trials comparing the 2 drugs are needed, as well as expanding data on discontinuation of therapy and/or consequential administration of them, with the aim to improve our clinical practise.

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Acquired resistance to the Hedgehog pathway inhibitor vismodegib due to smoothened mutations in treatment of locally advanced basal cell carcinoma

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2014.08.001 ◽

2014 ◽

Vol 71 (5) ◽

pp. 1005-1008 ◽

Cited By ~ 41

Author(s):

Tjinta Brinkhuizen ◽

Marie G. Reinders ◽

Michel van Geel ◽

Annelot J.L. Hendriksen ◽

Aimée D.C. Paulussen ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Locally Advanced ◽

Acquired Resistance ◽

Hedgehog Pathway ◽

Hedgehog Pathway Inhibitor ◽

Advanced Basal Cell Carcinoma

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The clinical impact of hedgehog pathway inhibitors and statin therapy in the treatment of locally advanced basal cell carcinoma: A case report

Dermatologic Therapy ◽

10.1111/dth.15191 ◽

2021 ◽

Author(s):

Luciana Trane ◽

Flavia Silvestri ◽

Federico Venturi ◽

Biancamaria Zuccaro ◽

Federica Scarfì ◽

...

Keyword(s):

Case Report ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Statin Therapy ◽

Basal Cell ◽

Locally Advanced ◽

Clinical Impact ◽

Hedgehog Pathway ◽

Advanced Basal Cell Carcinoma

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Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry

PLoS ONE ◽

10.1371/journal.pone.0262151 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0262151

Author(s):

Aleksandar Sekulic ◽

Simon Yoo ◽

Ragini Kudchadkar ◽

Julie Guillen ◽

Gary Rogers ◽

...

Keyword(s):

Clinical Trials ◽

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Basal Cell ◽

Real World ◽

Locally Advanced ◽

The United States ◽

Treatment Patterns ◽

Advanced Basal Cell Carcinoma

Background Limited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States. Methods This prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor–naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings. Results Determination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment. Conclusions This prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials.

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Basalzellkarzinom: Hedgehog-Pathway-Inhibitoren bei lokal fortgeschrittenen oder metastasierten Tumoren

Karger Kompass Dermatologie ◽

10.1159/000514103 ◽

2021 ◽

pp. 1-2

Author(s):

Jan Maschke

Keyword(s):

Basal Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Basal Cell ◽

Response Rate ◽

Objective Response ◽

Locally Advanced ◽

Hedgehog Pathway ◽

Oder Eine ◽

Advanced Basal Cell Carcinoma

Die Publikation von Dummer et al. beschreibt die Daten zur Effektivität und Sicherheit des Hedgehog pathway Inhibitors (HPI) Sonidegib in der abschließenden 42-Monatsanalyse der BOLT (basal cell carcinoma outcomes with LDE225 (sonidegib) treatment) Studie. Ursprünglich wurden 230 erwachsene, nicht systemisch mit HPI vorbehandelte Patienten mit Basalzellkarzinomen (BCC), die nicht für eine kurative chirurgische Behandlung oder eine Bestrahlung in Frage kamen, in 58 Zentren aus 12 Ländern zwischen dem 20. Juli 2011 und dem 10. Januar 2013 eingeschlossen. Die primäre Datenanalyse fand 6 Monate nach der Randomisierung des letzten Patienten statt. Diese wurden im Verhältnis 1:2 für die Behandlung mit 200mg (n = 79) oder 800mg (n = 151) Sonidegib pro Tag per os randomisiert. Auf eine zweckmäßige Vergleichstherapie wurde verzichtet, weil bei diesen Patienten mit lokal fortgeschrittenem Basalzellkarzinom (locally advanced Basal Cell Carcinoma, laBCC) oder metastasiertem Basalzellkarzinom (mBCC) keine Spontanremission zu erwarten sei und bei Beginn der Studie kein geeigneter Komparator zur Verfügung stand (die Zulassung von Vismodegib als HPI beim BCC erfolgte 2013). Die Behandlung erfolgte bis zum Fortschreiten der Erkrankung, dem Auftreten von nicht tolerabler Toxizität, bis zum Studienende, dem Rückzug des Einverständnisses oder dem Versterben der Patienten. In Bezug auf die Effektivität wurde das objektivierbare Tumoransprechen (Objective Response Rate, ORR) bei laBCC anhand von modifizierten RECIST (mRECIST) Kriterien durch ein zentrales Gutachterboard bewertet oder mithilfe der RECIST Kriterien bei mBCC. Die Sicherheitsanalyse wurde über die kontinuierliche Dokumentation und Überwachung der unerwünschten Ereignisse (adverse events, AE) vorgenommen.

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