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 Dermato Oncology University Hospital Nantes Hotel Dieu Place Alexis Ricordeau 44093 Cedex 01 Nantes France

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

Department of Oncology Pathology Karolinska University Hospital Hospital Solma 171 76 Stockholm Sweden

Dermatology and Oncology Service Aix Marseille University and Timone Hospital 264 Rue St Pierre 13385 Cedex 05 Marseille France

Dermatology Department Charles University 3rd Faculty of Medicine Šrobárova 1150 50 100 34 Praha 10 Prague Czech Republic

Dermatology Department of Diagnostic Experimental and Specialty Medicine University of Bologna Via Massarenti 1 40138 Bologna Italy

Dermatology Department University Hospital of Montpellier 80 Avenue Augustin Fliche 34090 Montpellier France

Dermatology Department University Hospital Zurich Gloriastr 31 8091 Zurich Switzerland

Dermatology Service Centre Hospitalier Universitaire de Lyon Centre Hospitalier Lyon Sud 69495 Pierre Bénite Lyon France

Dermatology Service University Hospital of Bordeaux 1 Rue Jean Burguet 33075 Bordeaux France

Dermatology Service University of Lille 2 Lille Regional University Hospital Hôpital Huriez 2 Avenue Oscar Lambret 59037 Lille France

Fondazione IRCCS Istituto Nazionale dei Tumori Milan and University of Milan Via Giacomo Venezian 1 20133 Italy

Melanoma Cancer Immunotherapy and Innovative Therapy Unit Istituto Nazionale Tumori Fondazione Pascale Via Mariano Semmola 80131 Naples Italy

Oncology Centre Addenbrooke's Hospital Hills Road Cambridge CB2 2OQ UK

Oncology Department Instituto Portugues de Oncologia R Dr António Bernardino de Almeida 4200 072 Porto Portugal

Roche Products Ltd 6 Falcon Way Shire Park Welwyn Garden City Hertfordshire AL7 1TW UK

Skin Cancer Unit Paul Sabatier University and Toulouse University Cancer Institute 24 Chemin de Pouvourville TSA30030 31059 Toulouse France

University Dermatology Clinic Medical University of Vienna Währinger Gürtel 18 20 A 1090 Vienna Austria

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ClinicalTrials.gov
NCT01367665, NCT01367665