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Efficacy and Safety of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: An Updated Systematic Review and Meta-analysis (2009-2022).
- Source :
-
American journal of clinical dermatology [Am J Clin Dermatol] 2023 May; Vol. 24 (3), pp. 359-374. Date of Electronic Publication: 2023 Feb 16. - Publication Year :
- 2023
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Abstract
- Background: Basal cell carcinoma (BCC) of the skin is the most common form of skin cancer in the United States. In life-threatening, advanced BCC, sonic hedgehog inhibitors (SSHis) remain a pre-eminent treatment option for locally advanced BCC and metastatic BCC.<br />Objective: In this updated systematic review and meta-analysis, we aimed to better characterize the efficacy and safety of SSHis by including final updates from pivotal clinical trials and additional new recent studies.<br />Methods: An electronic database search was performed for articles including clinical trials, prospective case series, and retrospective medical record reviews on human subjects. Overall response rates (ORRs) and complete response rates (CRRs) were the primary outcomes. For safety assessment, the prevalence of the following adverse effects was analyzed: muscle spasms, dysgeusia, alopecia, weight loss, fatigue, nausea, myalgias, vomiting, skin squamous cell carcinoma, increased creatine kinase, diarrhea, decreased appetite, and amenorrhea. Analyses were performed using R statistical software. Data were pooled using linear models with fixed effects meta-analysis for primary analyses, along with 95% confidence intervals (CIs) and p-values. Intermolecular differences were calculated using Fisher's exact test.<br />Results: A total of 22 studies (N = 2384 patients) were included in the meta-analysis: 19 studies assessing both efficacy and safety, 2 studies assessing safety only, and 1 study assessing efficacy only. Overall, the pooled ORR for all patients was 64.9% (95% CI 48.2-81.6%), implicating there is at least a partial response (z = 7.60, p < 0.0001) in most patients receiving SSHis. The ORR for vismodegib was 68.5% and 50.1% for sonidegib. The most common adverse effects for vismodegib and sonidegib were muscle spasms (70.5% and 61.0%, respectively), dysgeusia (58.4% and 48.6%, respectively), and alopecia (59.9% and 51.1%, respectively). Patients were likely to experience weight loss (35.1%, p < 0.0001) from vismodegib. Alternatively, patients taking sonidegib experienced more nausea, diarrhea, increased creatine kinase levels, and decreased appetite compared with those receiving vismodegib.<br />Conclusion: SSHis are an effective treatment for advanced BCC disease. Given the high discontinuation rates, management of patient expectations is warranted for compliance and achieving long-term efficacy. It is essential to stay updated with the latest discoveries on the efficacy and safety of SSHis.<br /> (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Subjects :
- Female
Humans
Hedgehog Proteins
Dysgeusia chemically induced
Dysgeusia epidemiology
Dysgeusia drug therapy
Retrospective Studies
Anilides adverse effects
Spasm chemically induced
Spasm drug therapy
Diarrhea chemically induced
Diarrhea drug therapy
Alopecia chemically induced
Alopecia drug therapy
Nausea chemically induced
Weight Loss
Creatine Kinase therapeutic use
Antineoplastic Agents adverse effects
Carcinoma, Basal Cell drug therapy
Carcinoma, Basal Cell pathology
Skin Neoplasms pathology
Drug-Related Side Effects and Adverse Reactions
Subjects
Details
- Language :
- English
- ISSN :
- 1179-1888
- Volume :
- 24
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of clinical dermatology
- Publication Type :
- Report
- Accession number :
- 36795228
- Full Text :
- https://doi.org/10.1007/s40257-023-00763-x