1153P - Subgroup analysis of patients (pts) with Gorlin syndrome treated with vismodegib (VISMO) in the STEVIE study

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Skin Cancers
Presenter Nicole Basset-Seguin
Citation Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379
Authors N. Basset-Seguin1, J. Hansson2, R. Kunstfeld3, J.J. Grob4, B. Dreno5, L. Mortier6, P.A. Ascierto7, N. Dimier8, A. Fittipaldo9, I. Xynos10, A. Hauschild11
  • 1Dermatology, Hôpital St. Louis, 75010 - Paris/FR
  • 2Department Of Oncology-pathology, Karolinska University Hospital, Stockholm/SE
  • 3Dermatology, Medical University of Vienna, Vienna/AT
  • 4Department Of Dermatology And Cutaneous Oncology, Aix-Marseille University, Hopital Timone APHM, Marseille/FR
  • 5Dermato Cancerology, Nantes University, Nantes/FR
  • 6Dermatology, University of Lille 2, Lille Regional University Hospital, Lille/FR
  • 7Melanoma, Cancer Immunotherapy, And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Napoli/IT
  • 8Department Of Biostatistics, Roche Products, Ltd., Welwyn Garden City/GB
  • 9Pharma Development, Roche Products, Ltd., AL7 1TW - Welwyn Garden City/GB
  • 10Product Development, Roche Products, Ltd., Welwyn Garden City/GB
  • 11Department Of Dermatology, University Hospital Schleswig-Holstein, 24105 - Kiel/DE



VISMO, a first-in-class Hedgehog pathway inhibitor, is approved (US and EU) in adults with locally advanced BCC (laBCC) or metastatic BCC (mBCC). STEVIE (ClinicalTrials.gov NCT1367665), is evaluating safety and efficacy of VISMO in pts with advanced BCC, including pts with Gorlin syndrome, a hereditary condition characterised by multiple BCCs. Data from the subset of Gorlin pts in the primary analysis are presented.


Pts with Gorlin syndrome could enrol in the study if they met protocol-defined criteria for laBCC or mBCC. Pts received oral VISMO 150 mg/day until progressive disease, unacceptable toxicity, or withdrawal. The primary outcome was safety. Secondary outcomes included efficacy and quality of life.


The analysis includes 219 Gorlin pts (laBCC, n = 214; mBCC, n = 5) with a median age of 52 (range 18–88) years. Median treatment duration was 374 days and median dose intensity was 95.8%. At cut-off (March 16, 2015), all Gorlin pts experienced ≥1 treatment-emergent adverse event (TEAE). Most common TEAEs were muscle spasm (78.1%), alopecia (78.1%), dysgeusia (58.0%), diarrhoea (30.6%), nausea (23.3%), fatigue (23.3%) and asthenia (20.5%). Most TEAEs (56%) were grade 1–2 and serious TEAEs were reported in 17.8% of pts. Treatment discontinuation due to TEAEs occurred in 29.2% of pts and included muscle spasms (8.2%), alopecia (6.8%) and dysgeusia (5.0%); most were grade 1–2 (20.6%). Five pts (2.3%) died due to grade 5 AEs (n = 4) and other reasons (n = 1). All grade 5 AEs presented with confounding factors and assessed as unrelated to VISMO per investigator. Best overall response (Response Evaluation Criteria in Solid Tumors version 1.1; investigator assessed) was 81.7% (95% confidence interval [CI] 75.8–86.6). Median time to response was 2.9 months (95% CI 2.8–3.7). Median progression-free survival was 32.5 months (95% CI 29.4–not estimable [NE]). Median duration of response was 28.8 months (95% CI 24.8–NE).


TEAES reported in Gorlin pts are similar to those observed in previous studies of VISMO. The results confirmed clinical efficacy of VISMO in Gorlin pts, and support the use of VISMO in this pt population.

Clinical trial identification


Legal entity responsible for the study





N. Basset-Seguin: Employment: Genentech Consultant/Advisory: Novartis, Roche, Leo Pharma, Galderma, Pierre Fabre Patents, Royalties, Other: Genentech Travel, Accommodation, Expenses: Roche, Galderma, Leo Pharma. J. Hansson: Consultant/Advisory: BMS, GSK, MSD/Merck, Novartis,Roche Pharma Trial Grants/Research Funding: Amgen, BMS, GSK, MSD/Merck, Novartis, Roche. R. Kunstfeld: Honoraria: Roche, Novartis, Menarini, Meda‐Pharma Consulting/Advisory Role: Roche, Novartis, Menarini, Meda‐Pharma, Spirig, Leo Pharma. J.J. Grob: Honoraria: GSK, Roche, BMS Consulting/Advisory: GSK, BMS, Roche, Amgen, Merck, Novartis Speaker Bureau: GSK Research: Roche, BMS Travel, Accommodations, Expenses: Roche. B. Dreno: Consulting/Advisory: BMS, GSK, Roche, Novartis Speaker Bureau: BMS, GSK, Roche Research: BMS, GSK Travel, Accommodations, Expenses: BMS, Roche. L. Mortier: Research funding (institution received): Roche, BMS, GSK, CSO, and Novartis. P.A. Ascierto: Consultant/Advisory: BMS, Roche/Genentech, MSD, Ventana, Novartis, Amgen, Array Research: BMS, Roche/Genentech, Ventana. N. Dimier: Employment: Roche Stock/Other Ownership: Roche, GSK. A. Fittipaldo: Employee, Stockholder: Hoffman-La Roche. I. Xynos: Advisory Board, Honoraria, Investigator: Roche/Genentech. A. Hauschild: Consulting/Advisory, Honoraria, Trial Grants: Amgen, BMS, Celgene, Eisai, GSK, MedImmune, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, Roche Pharma.