Current Perspectives in the Treatment of Locally Advanced Basal Cell Carcinoma

Abstract

Basal cell carcinoma (BCC) is the most common cancer in Caucasians, and its incidence continues to rise. Generally, BCCs have good outcomes when diagnosed and treated early. However, 1–10% of patients will develop advanced disease due to either delays in accessing treatment or aggressive tumors that may be refractory to treatment. Locally advanced basal cell carcinomas (laBCCs) are large, aggressive, or recurrent tumors that have the potential to invade surrounding tissues including bone, cartilage, nerve, and muscle. Treatment requires a multi-disciplinary approach where different modalities including surgery, radiation therapy, Hedgehog Pathway Inhibitors, and immunotherapy can be considered.

Efficacy and Safety of Cemiplimab for the Management of Non-Melanoma Skin Cancer: A Drug Safety Evaluation

“…BCC metastases are rare, while cSCC can metastasize in 3-7% of cases [7]. Surgical excision is the primary treatment for both, though Mohs micrographic surgery and various destructive therapies like topical drugs, radiation therapy, and cryotherapy are also used based on tumor and patient factors [7][8][9][10][11][12][13].…”

“…For BCC, understanding its pathogenesis, particularly the role of hedgehog (HH) signaling, led to hedgehog pathway inhibitors (HHIs) like sonidegib and vismodegib, which have shown effectiveness [7][8][9][10][11][12][13]. However, some patients do not respond well or tolerate HHIs, necessitating alternative treatments [7][8][9][10][11][12].…”

“…For BCC, understanding its pathogenesis, particularly the role of hedgehog (HH) signaling, led to hedgehog pathway inhibitors (HHIs) like sonidegib and vismodegib, which have shown effectiveness [7][8][9][10][11][12][13]. However, some patients do not respond well or tolerate HHIs, necessitating alternative treatments [7][8][9][10][11][12]. Similarly, despite the fact that cSCC are commonly treated with topical therapies or surgery, new systemic therapies are needed for metastatic (mcSCC) and locally advanced (lacSCC) [13,14].…”

Reinduction of Hedgehog Inhibitors after Checkpoint Inhibition in Advanced Basal Cell Carcinoma: A Series of 12 Patients

“…The PD1i cemiplimab has been approved since 2021 for patients with aBCC intolerant to or progressive on treatment with HHIs. PD1i increase the T-cell-mediated immune response, thereby sustaining the endogenous antitumor activity [ 5 , 6 ]. It has been found that 31% of patients with laBCC and 24% with mBCC will respond to second-line treatment with cemiplimab after HHI.…”

“…It has been found that 31% of patients with laBCC and 24% with mBCC will respond to second-line treatment with cemiplimab after HHI. Even though PD1i pembrolizumab is at present not approved for treatment of aBCC, small studies and case series suggest a similar response rate in aBCC pretreated with HHI compared to cemiplimab [ 5 , 6 , 7 , 8 ].…”