Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial
Language English Country Great Britain, England Media print-electronic
Document type Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
PubMed
29073584
DOI
10.1016/j.ejca.2017.08.022
PII: S0959-8049(17)31247-9
Knihovny.cz E-resources
- Keywords
- Basal cell carcinoma, Gorlin syndrome, Hedgehog pathway inhibitor, STEVIE, Vismodegib,
- MeSH
- Anilides administration & dosage adverse effects MeSH
- Administration, Oral MeSH
- Carcinoma, Basal Cell drug therapy mortality secondary MeSH
- Time Factors MeSH
- Adult MeSH
- Kaplan-Meier Estimate MeSH
- Creatine Kinase blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Disease-Free Survival MeSH
- Disease Progression MeSH
- Antineoplastic Agents administration & dosage adverse effects MeSH
- Pyridines administration & dosage adverse effects MeSH
- Drug Administration Schedule MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Spasm chemically induced MeSH
- Basal Cell Nevus Syndrome drug therapy mortality pathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anilides MeSH
- HhAntag691 MeSH Browser
- Creatine Kinase MeSH
- Antineoplastic Agents MeSH
- Pyridines MeSH
BACKGROUND: The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented. PATIENTS AND METHODS: Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points. RESULTS: Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC. CONCLUSIONS: The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. CLINICALTRIALS.GOV: NCT01367665.
Department of Dermatology Hôpital Saint Louis 1 Avenue Claude Vellefaux 75475 Paris France
Department of Dermatology University of Kiel Rosalind Franklin Str 7 D 24105 Kiel Germany
Dermatology Department University Hospital Zurich Gloriastr 31 8091 Zurich Switzerland
Dermatology Service University Hospital of Bordeaux 1 Rue Jean Burguet 33075 Bordeaux France
Oncology Centre Addenbrooke's Hospital Hills Road Cambridge CB2 2OQ UK
Roche Products Ltd 6 Falcon Way Shire Park Welwyn Garden City Hertfordshire AL7 1TW UK
References provided by Crossref.org
ClinicalTrials.gov
NCT01367665, NCT01367665
