Long-term strategies for management of advanced basal cell carcinoma with hedgehog inhibitors

Bossi, Paolo; Ascierto, Paolo A.; Basset-Séguin, Nicole; Dréno, Brigitte; Dummer, Reinhard; Hauschild, Axel; Mohr, Peter; Kaufmann, Roland; Pellacani, Giovanni; Puig, Susana; Moreno‐Ramírez, D.; Robert, Caroline; Stratigos, Alexander; Gutzmer, Ralf; Queirolo, Paola; Quaglino, Pietro; Peris, Ketty

doi:10.1016/j.critrevonc.2023.104066

Cited by 14 publications

(3 citation statements)

References 67 publications

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“…Immunotherapy is only indicated in laBCC in second line after progression to hedgehog inhibitors or after unacceptable toxicities to them. 7 …”

Section: Discussionmentioning

confidence: 99%

Complete response of metastatic cutaneous squamous cell carcinoma and multiple locally advanced basal cell carcinomas with concomitant pembrolizumab and sonidegib therapy

González-Cruz,

Muñoz-Couselo,

Ortiz-Velez

et al. 2024

JAAD Case Reports

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“…Immunotherapy is only indicated in laBCC in second line after progression to hedgehog inhibitors or after unacceptable toxicities to them. 7 …”

Section: Discussionmentioning

confidence: 99%

Complete response of metastatic cutaneous squamous cell carcinoma and multiple locally advanced basal cell carcinomas with concomitant pembrolizumab and sonidegib therapy

González-Cruz,

Muñoz-Couselo,

Ortiz-Velez

et al. 2024

JAAD Case Reports

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“…Our case series proved the superiority in terms of effectiveness and safety of sonidegib over vismodegib in the treatment of BCCs in Gorlin syndrome. These data, together with the option of dose interruptions, supportive medications to better manage the adverse events, and on-label dose reduction for sonidegib to the “every other day” schedule [ 32 , 33 ], make this molecule a candidate for the long-term management of these chronic patients and one to be investigated with large, controlled trials. Since drug resistance may be caused by mutations that confer resistance to sonidegib or vismodegib [ 21 , 34 ], the development of new HHIs may also be significant.…”

Section: Discussionmentioning

confidence: 99%

Gorlin Syndrome-Associated Basal Cell Carcinomas Treated with Vismodegib or Sonidegib: A Retrospective Study

Murgia,

Valtellini,

Denaro

et al. 2024

Cancers

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Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway. The use of hedgehog pathway inhibitors—vismodegib and sonidegib—has emerged as a promising therapeutic strategy for managing BCCs in individuals with GS. In a retrospective study conducted between March 2012 and January 2024, a cohort of 16 Gorlin syndrome patients who received treatment with either sonidegib or vismodegib were analyzed. The primary objectives of the study were to evaluate the efficacy, safety profile, and duration of response to oral hedgehog inhibitors in this patient population. The study assessed various parameters, including the number of new BCCs that developed before and after treatment initiation, the duration and sustainability of treatment responses, as well as the incidence of adverse effects associated with hedgehog inhibitor therapy. The findings of the study revealed that sustained treatment with hedgehog inhibitors could effectively suppress the progression of both new and existing BCCs. Furthermore, the results indicated that sonidegib exhibited superior efficacy and safety compared to vismodegib in the treatment of BCCs in individuals with GS. Notably, adjustments to the administration schedule of sonidegib were found to improve tolerability without compromising therapeutic efficacy, potentially leading to prolonged durations of treatment response and disease control.

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“…The durability of response and long-term safety reinforce vismodegib’s clinical utility in advanced BCC cases where treatment options are limited. However, one of the challenges in the long-term use of vismodegib is the development of resistance, either through acquired mutations in the Smoothened (SMO) gene or the selection of pre-existing SMO mutations within the tumor ( 20 ). Secondary resistance is estimated to occur in 15-35% of patients who receive vismodegib as a retreatment after initial discontinuation due to relapse.…”

Section: Introductionmentioning

confidence: 99%

Case report: Sequential treatment strategy for advanced basal cell carcinoma in Gorlin-Goltz syndrome: integration of vismodegib, radiotherapy, surgery, and high-intensity focused ultrasound

Calik,

Oślizło,

Słocka-Romaniuk

et al. 2024

Front. Oncol.

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Managing advanced basal cell carcinoma (BCC) in patients with Gorlin-Goltz syndrome presents unique clinical challenges due to the tumor’s aggressive nature and potential for widespread metastasis. This case study details a sequential treatment regimen for a 68-year-old female patient with an extensive, inoperable BCC. Employing a multimodal approach that integrates radiotherapy, the Hedgehog pathway inhibitor vismodegib, and High-Intensity Focused Ultrasound (HIFU), we demonstrate the potential for nearly complete remission in a patient with advanced BCC. Initial treatment with radiotherapy and vismodegib reduced tumor size significantly, but the largest mass displayed resistance over time, signifying the need for innovative therapies. Subsequent HIFU treatment targeted individual lesions, showcasing a non-invasive method that provided precise treatment while mitigating systemic side effects. The case emphasizes the necessity of continual adaptation in treatment plans to address the development of resistance and underscores the importance of incorporating new technologies and targeted therapies for complex BCC cases. The successful outcome of this integrated strategy suggests a promising direction for future research and highlights the importance of multidisciplinary approaches that tailor treatment to individual patient needs, tumor characteristics, and evolving therapeutic landscapes.

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Long-term strategies for management of advanced basal cell carcinoma with hedgehog inhibitors

Cited by 14 publications

References 67 publications

Complete response of metastatic cutaneous squamous cell carcinoma and multiple locally advanced basal cell carcinomas with concomitant pembrolizumab and sonidegib therapy

Complete response of metastatic cutaneous squamous cell carcinoma and multiple locally advanced basal cell carcinomas with concomitant pembrolizumab and sonidegib therapy

Gorlin Syndrome-Associated Basal Cell Carcinomas Treated with Vismodegib or Sonidegib: A Retrospective Study

Case report: Sequential treatment strategy for advanced basal cell carcinoma in Gorlin-Goltz syndrome: integration of vismodegib, radiotherapy, surgery, and high-intensity focused ultrasound

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