Original article
Efficacy, safety, and comparison of sonic hedgehog inhibitors in basal cell carcinomas: A systematic review and meta-analysis

https://doi.org/10.1016/j.jaad.2018.07.004Get rights and content

Background

Sonic hedgehog inhibitors (SHHis) provide an additional treatment option for basal cell carcinomas (BCCs), especially for metastatic or locally advanced BCC. However, studies have been heterogeneous and lacked direct comparisons between molecules.

Objective

To determine the efficacy and safety of the class of molecules SHHi for treating BCC and to compare them individually.

Methods

We performed a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)–compliant systematic review of studies followed by a meta-analysis.

Results

Eighteen articles were included in our meta-analysis; 16 articles were combined for efficacy and 16 for safety. In locally advanced BCC, overall response rates (ORRs) were similar for vismodegib and sonidegib (69% vs 57%, respectively) but not complete response rates (31% vs 3%, respectively). In metastatic disease, the ORR of vismodegib was 2.7-fold higher than the ORR of sonidegib (39% vs 15%, respectively). For side effects affecting a majority of patients, prevalences for muscle spasms (67.1%), dysgeusia (54.1%), and alopecia (57.7%) were in similar proportions for sonidegib and vismodegib. Patients receiving sonidegib experienced more upper gastrointestinal distress than patients receiving vismodegib.

Conclusion

SHHis induce a partial response to locally advanced BCC disease. Side effects are common, similar across molecules, associated with high discontinuation rates, and warrant discussion beforehand.

Section snippets

Systematic review

This systematic review and meta-analysis followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.17 The study protocol was published prospectively by GitHub Inc (https://github.com/plefrancois/Meta_BCC_SHHi). Our search goal was to retrieve all studies involving the treatment of BCC with SHHis. We used ClinicalTrials.gov to determine which SHHis had been used to treat BCC. We performed a broad search in PubMed, ClinicalTrials.gov, Embase, and Cochrane

Systematic review

This study's flow diagram is shown in Supplemental Fig 1 (available at http://www.jaad.org). Fourteen studies focused on vismodegib,4, 12, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 2 on sonidegib,14, 33, 34 1 on itraconazole,16 and 1 on TAK-441.15 Table I presents efficacy data and Table II safety data for individual studies. Across all studies, median drug exposure ranged 1.3-21 (median 5.25) months and median follow-up time 1.3-36 (median 11) months.

Bias assessment

Among the 18 studies, 13 were

Discussion

Our meta-analysis reveals that clinicians should expect partial responses in laBCC with vismodegib or sonidegib treatment. Compared with sonidegib, vismodegib had a higher ORR and CRR for laBCC and higher ORR for mBCC. Moreover, sonidegib caused more upper gastrointestinal disturbances and myalgias than vismodegib. These findings favor the use of vismodegib over sonidegib in clinical practice. One small study reported that sequential therapy with sonidegib for vismodegib-resistant BCC is

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  • Cited by (0)

    Drs Xie and Lefrançois contributed to this work equally.

    Funding sources: Partly supported by the Canadian Dermatology Foundation.

    Conflicts of interest: None disclosed.

    Reprints not available from the authors.

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