Table 1. Summary of clinical studies and case reports on switching Hedgehog inhibitors.

Publication	Type	Patient characteristics	Treatment	Efficacy results	Safety results
Yoon et al. [42]	Case report	• 87-year-old male • Inoperable laBCC of ethmoid sinus and brain • Treated with vismodegib 150 mg/day 5 years earlier; acquired resistance after > 1 year, vismodegib was discontinued • Radiation therapy • Recurrence after 2 years • Progression on 6 months of vismodegib • Pembrolizumab (3 cycles) resulted in further progression	Sonidegib 200 mg/day + itraconazole pulse dosed at 100 mg/day for 2 weeks/rest for 2 weeks, repeated monthly	• Significant improvement after 3 months • After 8 months, intracranial lesion no longer visible, intranasal and sinus lesions stable/slightly improved	No major AEs
Tran et al. [43]	Clinical study	• laBCC or mBCC • Median (range) age at enrollment, 61 (45–87) years • 5 patients had received prior HHIs (vismodegib, taladegib)	Sonidegib 200 mg/day + buparlisib 80 mg/day, 28-day cycles	• Median (range) follow-up, 8 (0.5–20) months • 7 evaluable patients • ORR: 1/7 (14.3%) • PR/SD as best response: 5/7 (71%)	Grade 3 TRAEs 50% patients led to early study termination
Zargari et al. Dermatol Ther. 2017	Case report	• 48-year-old male • Infiltrative BCC on the nose excised incompletely • Recurrence and appearance of new lesions treated with radiation therapy • Recurrent lesion improved with imiquimod treatment • Recurrent lesion infiltrated the whole nose, visual limitation • Treated with itraconazole twice daily for 4 months with minimal effect	Vismodegib 150 mg/day for 3 consecutive 28-day cycles	• Significant decrease in size and signs of healing at 1 month, improved visual movement • No signs of recurrence 8 months after treatment	No significant AEs
Danial et al.[44]	Clinical study	• Advanced BCC with demonstrated intrinsic or acquired resistance to vismodegib • Mean (range) age, 57.4 (42–91) years	Sonidegib 800 mg/day, 28-day cycles	• Median (range) treatment duration, 6 (3–58) weeks • 5/9 patients had PD within a median of 6 weeks • 3/9 patients had SD within a median of 4 weeks • 1 patient discontinued treatment for grade 3 rhabdomyolysis	Grade 3 AEs: rhabdomyolysis, nausea, altered mental status
Zhu et al.[48]	Case report	• Male in his 50s • Gorlin syndrome • Multiple BCCs on the head, neck, trunk, and all 4 extremities • Cutaneous lesions shrank with saridegib 130 mg/day • Lung metastases were refractory to saridegib 130 mg/day	Vismodegib 150 mg/day	• Vismodegib 150 mg/day resulted in further shrinkage of cutaneous lesions • After 4 months of treatment, lung metastases had progressed	Not reported

Abbreviations: AE: adverse event; BCC: basal cell carcinoma; laBCC: locally advanced BCC; mBCC: metastatic BCC; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; TRAE: treatment-related adverse event.