Systemic treatments for managing advanced or metastatic BCC (mBCC) that cannot be treated with conventional methods, including Hedgehog pathway inhibitors and immunotherapy, are the cornerstones of treatment for these cases.1
In specific populations, such as the immune-suppressed, the elderly, those with poor baseline functional status, and cases of metastatic, advanced, recalcitrant, or cosmetically sensitive disease, nonsurgical management may be a desirable alternative.2 BCC rarely reaches an advanced stage, so systemic chemotherapy is not typically used to treat these cancers.3
Aberrant signaling in the Hedgehog pathway is a principal driver in BCC’s progression and pathogenesis.4
Vismodegib and sonidegib, hedgehog pathway inhibitors, have been FDA-approved for treatment (Table 1).
The effectiveness of these treatments is limited by the development of resistance, which reduces their efficacy.1 Additionally, these therapies often lead to serious adverse events, such as ageusia/dysgeusia, muscle spasms, alopecia, and weight loss, causing discontinuation.7 Therefore, according to the NCCN guidelines, drug holidays or alternative dosing schedules are recommended to manage side effects, improve adherence to therapy, and enhance the quality of life for patients. For patients who no longer benefit from or cannot tolerate hedgehog pathway inhibitors, immunotherapy with cemiplimab is recommended.1
Cemiplimab and pembrolizumab are immunotherapy drugs that target the PD-1 receptor on T cells. Normally, PD-L1 proteins on peripheral tissues and tumor cells bind to PD-1 receptors, sending inhibitory signals that suppress T cell activity and proliferation. By blocking this interaction, these drugs enhance the anti-tumor immune response of T cells, countering the immune-suppressive environment created by tumors.4
One small study also aimed to explore the combined effect of Hedgehog pathway inhibitors and immunotherapy, investigating pembrolizumab and vismodegib. Refer to the Immunotherapy in cSCC tab to review the study details.
Systemic treatments such as Hedgehog pathway inhibitors and immunotherapy show promise in managing advanced and metastatic BCC. While Hedgehog pathway inhibitors have proven effective, dealing with resistance and adverse effects remains challenging. It is crucial to follow treatment guidelines because there is still much to learn about the best use of existing systemic inhibitors of the hedgehog pathway and the discovery of new therapies that can achieve high response rates with fewer side effects. Determining the best treatment approach often requires input from multiple specialists, considering the individual patient’s condition and response to treatment.9
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