Hedgehog inhibitors with and without adjunctive therapy in treatment of locally advanced basal cell carcinoma

Background Hedgehog inhibitor therapy (HHIT) is considered first-line treatment for locally advanced, unresectable basal cell carcinoma (laBCC). HHIT often results in a partial response, which requires adjunctive therapy (AT) post HHIT. We present real-world data for laBCCs undergoing HHIT +/- AT. Methods Retrospective review at Duke University from 11/01/2007 through 5/20/2020 revealed 13 patients treated with systemic HHIT (sonidegib or vismodegib) for laBCC. Results Fourteen laBCCs were identified in 13 patients. LaBCCs were treated with sonidegib (n = 10, 71%) or vismodegib (n = 4, 29%) for a median (IQR) of 9.4 (9.3) or 9.8 (8.5) months, respectively. The median (IQR) follow-up time from HHIT initiation was 15.5 (8.7) months. Tumors were most often located on the trunk (43%), followed by head and neck (29%), extremities (21%), and orbit/periorbital area (7%). Nine laBCCs (64%) were treated with HHIT alone, of which five (36%) achieved complete response (CR), four (29%) achieved partial response (PR), and five (36%) achieved CR with combined HHIT and AT post-HHIT. Duration of HHIT treatment (IQR) was 7.5 (3.5) months in the 10 CR patients, versus 15.1 (6.3) months in the four PR patients (P = 0.024). Nine patients (69%) experienced adverse events from HHIT, most commonly ageusia/dysgeusia, muscle spasms, and alopecia. Conclusion As a single institutional experience, we report 10/14 laBCCs (71%) with CRs without recurrence and 4/14 laBCCs (29%) with PRs with HHIT +/- AT over median followup of 15.5 months. Longer follow-up and larger cohorts evaluating responses with HHIT followed by AT are needed to substantiate our findings.