Oncotarget published "Using drug scheduling to manage adverse events associated with hedgehog pathway inhibitors for basal cell carcinoma" which reported that Basal cell carcinoma is the most common malignancy and form of skin cancer worldwide; advanced BCC, either as locally advanced BCC or metastatic BCC, can cause substantial tissue invasion and morbidity.
Until the recent availability of the hedgehog pathway inhibitors sonidegib and vismodegib, treatment options for advanced BCC were limited.
These agents demonstrate efficacy in patients with laBCC and mBCC; however, the adverse events associated with these agents can lead to treatment interruption or discontinuation and reduced quality of life, all of which significantly impact long-term adherence to therapy, which might affect clinical outcome.
Given that most AEs are class-related effects, switching HHIs does not appear to lead to a significantly different AE profile, underscoring the importance of maintaining patients on their first HHI.
Interrupting treatment of sonidegib and vismodegib does not appear to undermine the efficacy of these agents and is therefore a practical option to manage AEs in order to maintain continued treatment and disease control.
Dr. John T. Lear from The University of Manchester said, "Basal cell carcinoma (BCC) is the most common malignancy and form of skin cancer worldwide."
Basal cell carcinoma (BCC) is the most common malignancy and form of skin cancer worldwide
BCC accounts for most of the approximately 3.5 million global annual diagnoses of nonmelanoma skin cancer.
BCC infrequently results in death or metastasis; however, advanced BCC, either as locally advanced BCC or metastatic BCC, can cause substantial tissue invasion and morbidity.
The hedgehog signaling pathway regulates normal cell development and proliferation and plays a key role in the development of BCC.
In particular, most BCCs are associated with upregulation of the hedgehog signaling pathway due to mutations in the human homologue of the Drosophila patched gene or smoothened protein.
Inhibition of the hedgehog signaling pathway is therefore a rational treatment option in patients with advanced BCC.
Vismodegib and sonidegib are hedgehog pathway inhibitors that selectively target SMO. These drugs are approved by the Food and Drug Administration and European Medicines Agency for treatment of laBCC that has recurred following surgery or radiation therapy or those who are not candidates for surgery or radiation therapy; vismodegib has also been approved by the FDA and EMA for mBCC, and both agents are approved for treatment of mBCC in Australia and Switzerland.
While the HHIs are important treatment advances for patients with advanced BCC, a population with previously limited treatment options, the safety profile of these agents significantly impacts long-term adherence to therapy.
Adverse events associated with HHIs can lead to treatment interruption or discontinuation and reduced quality of life, all of which might affect clinical outcome.
Given that most AEs are class related, switching HHIs does not appear to lead to a significantly different AE profile.
This underscores the importance of maintaining patients on their first HHI.
This article reviews the pivotal clinical trials in advanced BCC of vismodegib and sonidegib and provides clinical strategies for managing AEs to maximize benefit from therapy.
The Lear Research Team concluded in their Oncotarget Research Output, "The HHIs sonidegib and vismodegib are promising treatment options for patients with advanced BCC; however, AEs that occur during treatment with these agents can be difficult for patients to endure and can impact treatment adherence. Therefore, treatment with these agents needs to maintain a balance between disease control and potential adverse reactions. The common AEs observed in vismodegib and sonidegib clinical trials are class-related effects and include muscle spasm, alopecia, dysgeusia, nausea, decreased appetite, and fatigue. Muscle-related effects are also a class-related AE associated with HHIs, and therefore CK levels should be monitored. Additionally, monitoring electrolytes, renal function, and liver function tests is also an important part of treatment care for patients receiving HHIs. Treatment interruptions of vismodegib and sonidegib do not appear to negatively impact the efficacy of these agents and are a practical option for managing AEs in order to maintain a continued course of treatment."
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DOI - https://doi.org/10.18632/oncotarget.28145
Correspondence to - John T. Lear - [email protected]
Keywords -
adverse events,
basal cell carcinoma,
sonidegib,
hedgehog inhibitor,
drug scheduling
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