N Basset-Séguin1, A Hauschild2, R Kunstfeld3, J Grob4, B Dréno5, L Mortier6, P A Ascierto7, L Licitra8, C Dutriaux9, L Thomas10, N Meyer11, B Guillot12, R Dummer13, P Arenberger14, K Fife15, A Raimundo16, E Dika17, N Dimier18, A Fittipaldo19, I Xynos20, J Hansson21. 1. Department of Dermatology, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75475, Paris, France. Electronic address: nicole.basset-seguin@aphp.fr. 2. Department of Dermatology, University of Kiel, Rosalind-Franklin-Str 7, D-24105, Kiel, Germany. Electronic address: ahauschild@dermatology.uni-kiel.de. 3. University Dermatology Clinic, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. Electronic address: rainer.kunstfeld@meduniwien.ac.at. 4. Dermatology and Oncology Service, Aix Marseille University and Timone Hospital, 264 Rue St. Pierre, 13385, Cedex 05 Marseille, France. Electronic address: jean-jacques.grob@mail.ap-hm.fr. 5. Department of Dermato Oncology, University Hospital Nantes, Hotel Dieu, Place Alexis Ricordeau, 44093, Cedex 01 Nantes, France. Electronic address: brigitte.dreno@wanadoo.fr. 6. Dermatology Service, University of Lille 2, Lille Regional University Hospital, Hôpital Huriez, 2 Avenue Oscar Lambret, 59037, Lille, France. Electronic address: laurent.mortier@chru-lille.fr. 7. Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, Via Mariano Semmola, 80131, Naples, Italy. Electronic address: paolo.ascierto@gmail.com. 8. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, and University of Milan, Via Giacomo Venezian 1, 20133, Italy. Electronic address: lisa.licitra@istitutotumori.mi.it. 9. Dermatology Service, University Hospital of Bordeaux, 1 Rue Jean Burguet, 33075, Bordeaux, France. Electronic address: caroline.dutriaux@chu-bordeaux.fr. 10. Dermatology Service, Centre Hospitalier Universitaire de Lyon, Centre Hospitalier Lyon Sud, 69495, Pierre Bénite, Lyon, France. Electronic address: luc.thomas@chu-lyon.fr. 11. Skin Cancer Unit, Paul Sabatier University and Toulouse University Cancer Institute, 24 Chemin de Pouvourville TSA30030, 31059, Toulouse, France. Electronic address: meyer.n@chu-toulouse.fr. 12. Dermatology Department, University Hospital of Montpellier, 80 Avenue Augustin Fliche, 34090, Montpellier, France. Electronic address: b-quillot@chu-montpellier.fr. 13. Dermatology Department, University Hospital Zurich, Gloriastr. 31, 8091, Zurich, Switzerland. Electronic address: Reinhard.Dummer@usz.ch. 14. Dermatology Department, Charles University Third Faculty of Medicine, Šrobárova 1150/50, 100 34, Praha 10, Prague, Czech Republic. Electronic address: pa@avemedica.cz. 15. Oncology Centre, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2OQ, UK. Electronic address: kate.fife@addenbrookes.nhs.uk. 16. Oncology Department, Instituto Portugues de Oncologia, R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. Electronic address: anaraimundo@hotmail.com. 17. Dermatology, Department of Diagnostic, Experimental and Specialty Medicine, University of Bologna, Via Massarenti 1, 40138, Bologna, Italy. Electronic address: emi.dika3@unibo.it. 18. Roche Products Ltd., 6 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, UK. Electronic address: natalie.dimier@roche.com. 19. Roche Products Ltd., 6 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, UK. Electronic address: alberto.fittipaldo@roche.com. 20. Roche Products Ltd., 6 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, UK. Electronic address: xynosid@gmail.com. 21. Department of Oncology-Pathology, Karolinska University Hospital, Hospital Solma, 171 76, Stockholm, Sweden. Electronic address: Johan.Hansson@ki.se.
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.
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.
Authors: Vinodh Kakkassery; Steffen Emmert; Irenäus A Adamietz; György Kovács; Anselm M Jünemann; Caroline Otte; Michael Zimbelmann; Anton Brosig; Salvatore Grisanti; Ludwig M Heindl Journal: Ophthalmologe Date: 2020-02 Impact factor: 1.059