Abstract
The management of advanced basal cell carcinoma (aBCC), in contrast to non-advanced BCC, is often a significant challenge for patients and treating physicians. Nevertheless, sonic Hedgehog inhibitors and, more recently, immune checkpoint inhibitors have offered new hope for improved clinical outcomes. A thorough evaluation of the potential adverse effects of these systemic therapies is also crucial. This review provides detailed information on the clinical efficacy and safety of various regimens of sonic Hedgehog pathway inhibitors and immune checkpoint inhibitors in locally advanced basal cell carcinoma (laBCC) management over the last decade. Our systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We analyzed the data specific to patients with laBCC who received Hedgehog pathway and immune checkpoint inhibitors between 2013 and 2023 and presented the outcomes accordingly. Eleven articles were included in our systematic review, and ten articles were eligible for overall response rate (ORR) and complete response rate (CRR) meta-analysis. ORRs for vismodegib, sonidegib, cemiplimab, and nivolumab were 74%, 50%, 31%, and 17%, respectively. The complete response rate (CRR) was significantly higher for vismodegib at 40%, compared to sonidegib (2%) and cemiplimab (6%). The most common adverse effects of hedgehog pathway inhibitors include muscle spasms, dysgeusia, and alopecia, while cemiplimab is frequently associated with fatigue, diarrhea, and pruritus. The systemic therapies present a promising approach for the management of laBCC; however, their use is often limited by adverse effects. Among available options, vismodegib demonstrates superior ORR and CRR compared to sonidegib and immunotherapy, highlighting its potential as a preferred option.