Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial.

N Basset-Séguin, A Hauschild, R Kunstfeld, J Grob, B Dréno, L Mortier, P A Ascierto, L Licitra, C Dutriaux, L Thomas, N Meyer, B Guillot, R Dummer, P Arenberger, K Fife, A Raimundo, E Dika, N Dimier, A Fittipaldo, I Xynos, J Hansson

Journal: European journal of cancer (Oxford, England : 1990) 2017;86():334-348

PMID: 29073584

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Abstract

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.

Address: Department of Dermatology, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75475, Paris, France. Electronic address: [email protected].; Department of Dermatology, University of Kiel, Rosalind-Franklin-Str 7, D-24105, Kiel, Germany. Electronic address: [email protected].; University Dermatology Clinic, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. Electronic address: [email protected].; Dermatology and Oncology Service, Aix Marseille University and Timone Hospital, 264 Rue St. Pierre, 13385, Cedex 05 Marseille, France. Electronic address: [email protected].; Department of Dermato Oncology, University Hospital Nantes, Hotel Dieu, Place Alexis Ricordeau, 44093, Cedex 01 Nantes, France. Electronic address: [email protected].; Dermatology Service, University of Lille 2, Lille Regional University Hospital, Hôpital Huriez, 2 Avenue Oscar Lambret, 59037, Lille, France. Electronic address: [email protected].; Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, Via Mariano Semmola, 80131, Naples, Italy. Electronic address: [email protected].; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, and University of Milan, Via Giacomo Venezian 1, 20133, Italy. Electronic address: [email protected].; Dermatology Service, University Hospital of Bordeaux, 1 Rue Jean Burguet, 33075, Bordeaux, France. Electronic address: [email protected].; Dermatology Service, Centre Hospitalier Universitaire de Lyon, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, Lyon, France. Electronic address: [email protected].; Skin Cancer Unit, Paul Sabatier University and Toulouse University Cancer Institute, 24 Chemin de Pouvourville TSA30030, 31059, Toulouse, France. Electronic address: [email protected].; Dermatology Department, University Hospital of Montpellier, 80 Avenue Augustin Fliche, 34090, Montpellier, France. Electronic address: [email protected].; Dermatology Department, University Hospital Zurich, Gloriastr. 31, 8091, Zurich, Switzerland. Electronic address: [email protected].; Dermatology Department, Charles University Third Faculty of Medicine, Šrobárova 1150/50, 100 34, Praha 10, Prague, Czech Republic. Electronic address: [email protected].; Oncology Centre, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2OQ, UK. Electronic address: [email protected].; Oncology Department, Instituto Portugues de Oncologia, R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. Electronic address: [email protected].; Dermatology, Department of Diagnostic, Experimental and Specialty Medicine, University of Bologna, Via Massarenti 1, 40138, Bologna, Italy. Electronic address: [email protected].; Roche Products Ltd., 6 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, UK. Electronic address: [email protected].; Roche Products Ltd., 6 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, UK. Electronic address: [email protected].; Roche Products Ltd., 6 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, UK. Electronic address: [email protected].; Department of Oncology-Pathology, Karolinska University Hospital, Hospital Solma, 171 76, Stockholm, Sweden. Electronic address: [email protected].

DOI: 10.1016/j.ejca.2017.08.022

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MeSH Terms: Administration, Oral, Adolescent, Adult, Aged, Aged, 80 and over, Anilides, Antineoplastic Agents, Basal Cell Nevus Syndrome, Carcinoma, Basal Cell, Creatine Kinase, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Pyridines, Spasm, Time Factors, Treatment Outcome, Young Adult