For patients with advanced basal cell carcinoma (BCC), including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) such as vismodegib and sonidegib are approved as first-line systemic treatments. However, clinical trials have shown high discontinuation rates for these treatments—88% to 92% with vismodegib and around 92% with sonidegib. The primary factors for discontinuation are efficacy and adverse events. About half of the patients discontinue HHI after 8 to 12 months, often switching to immunotherapy, which is indicated in patients previously treated with an HHI or for whom an HHI is not appropriate (Figure).1,2
Cemiplimab, an anti–PD-1 agent, was the first immunotherapy to receive full FDA-approval for laBCC and accelerated approval for mBCC as a second-line therapy for patients previously treated with an HHI or for whom an HHI is not appropriate. In studies, cemiplimab has shown efficacy with a safety profile similar to other anti–PD-1 agents in advanced malignancies, including advanced and metastatic BCC.3
A pivotal study for cemiplimab, Study 1620 (NCT03132636) was an open-label, multi-center, non-randomized trial, including participants with advanced BCC (laBCC or mBCC) who had progressed on HHI therapy, had no objective response after 9 months on HHI therapy, or were intolerant of prior HHI therapy. Treatment consisted of cemiplimab 350 mg every 3 weeks for up to 93 weeks until disease progression, unacceptable toxicity, or completion of planned treatment.3,4
One small study aimed to explore the combined effect of Hedgehog pathway inhibitors and immunotherapy, investigating pembrolizumab and vismodegib5:
Currently, there are no approved neoadjuvant treatments for advanced BCC. However, neoadjuvant anti-PD-1 immunotherapy is being investigated in several clinical trials.1
Ongoing Clinical Trials for Neoadjuvant Immunotherapy:
Currently, no guidelines recommend adjuvant anti-PD-1 treatment for resected advanced BCC outside of clinical trials. The use of these therapies remains under investigation to better understand their efficacy and safety in the neoadjuvant setting (Table).1
Anti-PD-1 agents are a therapeutic option for advanced BCC patients not amenable to curative surgery or radiotherapy who have progressed or are intolerant to HHIs. Despite durable responses in some patients, many do not respond or lose their response to treatment. There is currently no validated predictive biomarker to select patients most likely to benefit from anti-PD-1 immunotherapy, underscoring the need for further research into personalized treatment approaches. Identifying and treating patients more likely to respond to anti-PD-1 therapy is a promising area of active research.1
