Treatment of Advanced Basal Cell Carcinoma with Sonidegib: Perspective from the 30-Month Update of the BOLT Trial

Chen, Leon; Aria, Alexander B.; Silapunt, Sirunya; Lee, Heng-Huan; Migden, Michael R.

doi:10.2217/fon-2017-0457

Cited by 26 publications

(19 citation statements)

References 50 publications

(68 reference statements)

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“…No additional efficacy was found from 800-mg dosing over the 200-mg dose. At 30-month follow-up, objective response rates in the 200-mg group were sustained at 56.1% for laBCC and 7.7% for Mbcc [ 64 ]. The 200-mg dose also exhibited a more benign side effect profile, with a lower rate of grade 3/4 adverse events (31% vs. 56%) and adverse events leading to drug discontinuation (22% vs. 36%) or dose reduction/interruption (32% vs. 60%) [ 65 ].…”

Section: Hedgehog Pathway Inhibitorsmentioning

confidence: 99%

Basal Cell Carcinoma: A Comprehensive Review

Dika

Scarfì

Ferracin

et al. 2020

IJMS

116

107

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Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge.

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Section: Hedgehog Pathway Inhibitorsmentioning

confidence: 99%

Basal Cell Carcinoma: A Comprehensive Review

Dika

Scarfì

Ferracin

et al. 2020

IJMS

116

107

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“…Alopecia with diffuse loss of hair density could also be observed; it affects the scalp, but also the eyebrows, eyelashes, and beard. The use of minoxidil 2-5% can be helpful [48].…”

Section: Management Of Adverse Eventsmentioning

confidence: 99%

Sonidegib: Safety and Efficacy in Treatment of Advanced Basal Cell Carcinoma

Villani

Fabbrocini

Costa

et al. 2020

Dermatol Ther (Heidelb)

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Hedgehog inhibitors are promising alternative treatments for patients with advanced basal cell carcinomas. Sonidegib (Odomzo Ò ), an oral smoothened (SMO) antagonist, is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) who present recurrence following surgery or radiation therapy, or those who are not candidates for surgery or radiotherapy. Several studies and randomized controlled trials have been conducted to evaluate the efficacy, safety, and tolerability of this new molecule that has demonstrated a good response rate (44%). Grade 1-2 adverse events have also been repor-ted. Further studies of real-world experiences are needed to better understand the correct management of the drug, alternative dosing regimens, and differences with other hedgehog inhibitors. This article provides a complete overview of the pharmacology and pharmacokinetics of sonidegib and a report of the trials and studies conducted. The most frequent adverse events and their correct management are also discussed.

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“…Importantly, in a preclinical model of medulloblastoma, patidegib was effective on tumors resistant to vismodegib [82], suggesting a lack of cross-resistance in all instances. Additionally, binding of HHIs to mutant forms of Smo revealed that a mutation at residue 518 increased affinity for sonidegib, while concomitantly decreasing affinity for vismodegib [83,84].…”

Section: Mechanisms Of Resistancementioning

confidence: 99%

Hedgehog signaling inhibitors in solid and hematological cancers

Cortes

Gutzmer

Kieran

et al. 2019

Cancer Treatment Reviews

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Background: The hedgehog signaling pathway is normally tightly regulated. Mutations in hedgehog pathway components may lead to abnormal activation. Aberrantly activated hedgehog signaling plays a major role in the development of solid and hematological cancer. In recent years, inhibitors have been developed that attenuate hedgehog signaling; 2 have been approved for use in basal cell carcinoma (BCC), while others are under development or in clinical trials. The aim of this review is to provide an overview of known hedgehog inhibitors (HHIs) and their potential for the treatment of hematological cancers and solid tumors beyond BCC. Design: Published literature was searched to identify articles relating to HHIs in noncutaneous cancer. Both preclinical and clinical research articles were included. In addition, relevant clinical trial results were identified from www.clinicaltrials.gov. Information on the pharmacology of HHIs is also included. Results: HHIs show activity in a variety of solid and hematological cancers. In preclinical studies, HHIs demonstrated efficacy in pancreatic cancer, rhabdomyosarcoma, breast cancer, and acute myeloid leukemia (AML). In clinical studies, HHIs showed activity in medulloblastoma, as well as prostate, pancreatic, and hematological cancers. Current clinical trials testing the efficacy of HHIs are underway for prostate, pancreatic, and breast cancers, as well as multiple myeloma and AML. Conclusions: As clinical trial results become available, it will be possible to discern which additional tumor types are suited to HHI mono-or combination therapy with other anticancer agents. The latter strategy may be useful for delaying or overcoming drug resistance. Dysregulated hedgehog signaling and the development of cancer The HH signaling pathway is normally tightly regulated; however, dysregulation due to mutations in Smo or Ptch1 plays a major role in

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Treatment of Advanced Basal Cell Carcinoma with Sonidegib: Perspective from the 30-Month Update of the BOLT Trial

Cited by 26 publications

References 50 publications

Basal Cell Carcinoma: A Comprehensive Review

Basal Cell Carcinoma: A Comprehensive Review

Sonidegib: Safety and Efficacy in Treatment of Advanced Basal Cell Carcinoma

Hedgehog signaling inhibitors in solid and hematological cancers

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