INTRODUCTION
For the majority of basal cell carcinomas (BCCs), surgery is the standard of treatment with an excellent prognosis, as recommended by the American Academy of Dermatology and the European consensus-based interdisciplinary guidelines.1,2 When surgery is contraindicated or unlikely to be effective, as in cases of locally advanced BCC (laBCC) or metastatic BCC (mBCC), systemic Hedgehog inhibitors (HHIs) are recommended.1-3
Two inhibitors of Smoothened, a Hedgehog pathway protein, are currently approved for treatment of advanced BCC. Sonidegib (Odomzo®; Sun Pharmaceutical Industries, Inc.; Cranbury, NJ) is approved in the US for the treatment of adults with laBCC that has recurred following surgery or radiation therapy, or for patients who are not candidates for surgery or radiation therapy.4 In the EU, Switzerland, and Australia, sonidegib is approved for the treatment of adults with laBCC who are not amenable to curative surgery or radiation therapy.5-7 Sonidegib is also indicated for mBCC in Switzerland and Australia.6,7 Vismodegib (Erivedge®; Genentech, Inc.; San Francisco, CA) is approved in the US for the treatment of adults with mBCC, or laBCC that has recurred after surgery, or for those who are not candidates for surgery or radiotherapy.8 In the EU, Switzerland, and Australia, it is indicated for adults with mBCC or laBCC inappropriate for surgery or radiotherapy.9,10 In the absence of head-to-head clinical studies, this review summarizes and juxtaposes published reports to date on the efficacy, safety, and pharmacokinetics (PK) of sonidegib and vismodegib.
Two inhibitors of Smoothened, a Hedgehog pathway protein, are currently approved for treatment of advanced BCC. Sonidegib (Odomzo®; Sun Pharmaceutical Industries, Inc.; Cranbury, NJ) is approved in the US for the treatment of adults with laBCC that has recurred following surgery or radiation therapy, or for patients who are not candidates for surgery or radiation therapy.4 In the EU, Switzerland, and Australia, sonidegib is approved for the treatment of adults with laBCC who are not amenable to curative surgery or radiation therapy.5-7 Sonidegib is also indicated for mBCC in Switzerland and Australia.6,7 Vismodegib (Erivedge®; Genentech, Inc.; San Francisco, CA) is approved in the US for the treatment of adults with mBCC, or laBCC that has recurred after surgery, or for those who are not candidates for surgery or radiotherapy.8 In the EU, Switzerland, and Australia, it is indicated for adults with mBCC or laBCC inappropriate for surgery or radiotherapy.9,10 In the absence of head-to-head clinical studies, this review summarizes and juxtaposes published reports to date on the efficacy, safety, and pharmacokinetics (PK) of sonidegib and vismodegib.
METHODOLOGY OF MAJOR CLINICAL STUDIES
Pivotal Studies in Advanced Basal Cell Carcinoma
The pivotal studies evaluating efficacy and safety of sonidegib and vismodegib in advanced BCC were BOLT (Basal Cell Carcinoma Outcomes with LDE225 [sonidegib] Treatment) for sonidegib, and ERIVANCE-BCC for vismodegib (Table 1). BOLT was a phase 2, randomized, double-blind, multicenter, adaptive clinical study, while ERIVANCE was a phase 2, single-arm, 2-cohort clinical study.11,12
Eligibility Criteria
Eligible patients in BOLT were ≥18 years old with an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
The pivotal studies evaluating efficacy and safety of sonidegib and vismodegib in advanced BCC were BOLT (Basal Cell Carcinoma Outcomes with LDE225 [sonidegib] Treatment) for sonidegib, and ERIVANCE-BCC for vismodegib (Table 1). BOLT was a phase 2, randomized, double-blind, multicenter, adaptive clinical study, while ERIVANCE was a phase 2, single-arm, 2-cohort clinical study.11,12
Eligibility Criteria
Eligible patients in BOLT were ≥18 years old with an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.