A Review of Hedgehog Inhibitors Sonidegib and Vismodegib for Treatment of Advanced Basal Cell Carcinoma

February 2021 | Volume 20 | Issue 2 | Original Article | 156 | Copyright © February 2021

Published online January 21, 2021

Michael Migden MD,a Aaron S. Farberg MD,b Reinhard Dummer MD,c Nicholas Squittieri MD,d C. William Hanke MDe

aDepartments of Dermatology and Head and Neck Surgery, The University of Texas–MD Anderson Cancer Center, Houston, TX
bSection of Dermatology, Baylor University Medical Center, Dallas, TX
cDepartment of Dermatology, University of Zürich, Skin Cancer Center, University Hospital, Zürich, Switzerland
dSun Pharmaceutical Industries, Inc., Princeton, NJ
eAscension Saint Vincent Hospital, Indianapolis, IN

by central review of 56% in laBCC and 8% in mBCC for the 200 mg group, and 46% in laBCC and 17% in mBCC for the 800 mg group (Table 2 and Figure 1). CR by central review reached 5% and 2% for patients with laBCC in the 200 mg and 800 mg groups, respectively, while CR for mBCC was 0% in both dose groups. Investigator-assessed ORR was 71% in laBCC and 23% in mBCC for the 200 mg group, with CR of 9% in laBCC and 0% in mBCC.11 Using RECIST criteria, ORR by central review for patients with laBCC was 59.5% and 55.9% for the 200 and 800 mg groups, respectively, and CR was achieved by 19.0% and 33.3% of patients receiving 200 and 800 mg, respectively.

A total of 96 patients were included in the ERIVANCE efficacy analysis (63 with laBCC and 33 with mBCC), who were 61% male with median age of 62 years.14 Eight patients with laBCC were excluded from the efficacy analysis because the diagnosis was not confirmed by an independent pathologist; these patients were included in the overall population. At 39 months, 8 (8%) patients remained on study treatment; the most common reason for discontinuation was disease progression, seen in 28 (28%) patients.12 The ERIVANCE final analysis reported investigator-assessed ORR of 60% and 49%, including CR of 32% and 0%, for patients with laBCC and mBCC, respectively (Table 2 and Figure 1).12

A secondary analysis of ERIVANCE examined baseline disease severity and clinical benefit of vismodegib treatment in 61
patients with laBCC.18 An independent review committee scored lesion photographs on a 5-point scale from 1 (no scarring and no functional impairment at baseline; significant worsening after treatment) to 5 (considerable deformity and functional impairment at baseline; significant clinical benefit after treatment). The majority of patients exhibited severe or moderate disease at baseline (59% scored 5, 13% scored 4), and significant or some clinical benefit after treatment (65% scored 5, 11% scored 4).18