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 & 1 others J Hansson

Research output: Contribution to journalArticle

43 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)334-348
Number of pages15
JournalEuropean Journal of Cancer
Volume86
DOIs
Publication statusPublished - Nov 2017

Fingerprint

HhAntag691
Basal Cell Carcinoma
Safety
Research Personnel
Basal Cell Nevus Syndrome
Confidence Intervals
Patient Advocacy
Incidence
Spasm
Creatine Kinase

Keywords

  • 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
  • Clinical Trial
  • Journal Article
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

Cite this

Basset-Séguin, N., Hauschild, A., Kunstfeld, R., Grob, J., Dréno, B., Mortier, L., ... Hansson, J. (2017). Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial. European Journal of Cancer, 86, 334-348. https://doi.org/10.1016/j.ejca.2017.08.022

Vismodegib in patients with advanced basal cell carcinoma : Primary analysis of STEVIE, an international, open-label trial. / Basset-Séguin, N; Hauschild, A; Kunstfeld, R; Grob, J; Dréno, B; Mortier, L; Ascierto, P A; Licitra, L; Dutriaux, C; Thomas, L; Meyer, N; Guillot, B; Dummer, R; Arenberger, P; Fife, K; Raimundo, A; Dika, E; Dimier, N; Fittipaldo, A; Xynos, I; Hansson, J.

In: European Journal of Cancer, Vol. 86, 11.2017, p. 334-348.

Research output: Contribution to journalArticle

Basset-Séguin, N, Hauschild, A, Kunstfeld, R, Grob, J, Dréno, B, Mortier, L, Ascierto, PA, Licitra, L, Dutriaux, C, Thomas, L, Meyer, N, Guillot, B, Dummer, R, Arenberger, P, Fife, K, Raimundo, A, Dika, E, Dimier, N, Fittipaldo, A, Xynos, I & Hansson, J 2017, 'Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial', European Journal of Cancer, vol. 86, pp. 334-348. https://doi.org/10.1016/j.ejca.2017.08.022
Basset-Séguin, N ; Hauschild, A ; Kunstfeld, R ; Grob, J ; Dréno, B ; Mortier, L ; Ascierto, P A ; Licitra, L ; Dutriaux, C ; Thomas, L ; Meyer, N ; Guillot, B ; Dummer, R ; Arenberger, P ; Fife, K ; Raimundo, A ; Dika, E ; Dimier, N ; Fittipaldo, A ; Xynos, I ; Hansson, J. / Vismodegib in patients with advanced basal cell carcinoma : Primary analysis of STEVIE, an international, open-label trial. In: European Journal of Cancer. 2017 ; Vol. 86. pp. 334-348.
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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.",
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author = "N Basset-S{\'e}guin and A Hauschild and R Kunstfeld and J Grob and B Dr{\'e}no and L Mortier and Ascierto, {P A} and L Licitra and C Dutriaux and L Thomas and N Meyer and B Guillot and R Dummer and P Arenberger and K Fife and A Raimundo and E Dika and N Dimier and A Fittipaldo and I Xynos and J Hansson",
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year = "2017",
month = "11",
doi = "10.1016/j.ejca.2017.08.022",
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TY - JOUR

T1 - Vismodegib in patients with advanced basal cell carcinoma

T2 - Primary analysis of STEVIE, an international, open-label trial

AU - Basset-Séguin, N

AU - Hauschild, A

AU - Kunstfeld, R

AU - Grob, J

AU - Dréno, B

AU - Mortier, L

AU - Ascierto, P A

AU - Licitra, L

AU - Dutriaux, C

AU - Thomas, L

AU - Meyer, N

AU - Guillot, B

AU - Dummer, R

AU - Arenberger, P

AU - Fife, K

AU - Raimundo, A

AU - Dika, E

AU - Dimier, N

AU - Fittipaldo, A

AU - Xynos, I

AU - Hansson, J

N1 - Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

KW - Administration, Oral

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Anilides

KW - Antineoplastic Agents

KW - Basal Cell Nevus Syndrome

KW - Carcinoma, Basal Cell

KW - Creatine Kinase

KW - Disease Progression

KW - Disease-Free Survival

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Pyridines

KW - Spasm

KW - Time Factors

KW - Treatment Outcome

KW - Young Adult

KW - Clinical Trial

KW - Journal Article

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ejca.2017.08.022

DO - 10.1016/j.ejca.2017.08.022

M3 - Article

VL - 86

SP - 334

EP - 348

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -