Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: Final update of the pivotal ERIVANCE BCC study

and for the ERIVANCE BCC Investigators

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Background: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. Methods: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. Results: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib. Conclusions: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. Trial registration: This study was registered prospectively with Clinicaltrials.gov , number NCT00833417on January 30, 2009.

Original languageEnglish (US)
Article number332
JournalBMC Cancer
Volume17
Issue number1
DOIs
StatePublished - May 16 2017

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HhAntag691
Basal Cell Carcinoma
Safety
Research Personnel
Survival
United States Food and Drug Administration
Disease-Free Survival

Keywords

  • Basal cell carcinoma (BCC)
  • Efficacy
  • Long-term
  • Safety
  • Vismodegib

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma : Final update of the pivotal ERIVANCE BCC study. / and for the ERIVANCE BCC Investigators.

In: BMC Cancer, Vol. 17, No. 1, 332, 16.05.2017.

Research output: Contribution to journalArticle

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title = "Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: Final update of the pivotal ERIVANCE BCC study",
abstract = "Background: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30{\%} and 43{\%} in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45{\%} (mBCC) and 60{\%} (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. Methods: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. Results: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5{\%} in the mBCC group (all partial responses) and 60.3{\%} in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7{\%}) were reported; none were related to vismodegib. Conclusions: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. Trial registration: This study was registered prospectively with Clinicaltrials.gov , number NCT00833417on January 30, 2009.",
keywords = "Basal cell carcinoma (BCC), Efficacy, Long-term, Safety, Vismodegib",
author = "{and for the ERIVANCE BCC Investigators} and Sekulic, {Aleksandar D} and Migden, {Michael R.} and Nicole Basset-Seguin and Claus Garbe and Anja Gesierich and Lao, {Christopher D.} and Chris Miller and Laurent Mortier and Murrell, {Dedee F.} and Omid Hamid and Quevedo, {Jorge F.} and Jeannie Hou and Edward McKenna and Natalie Dimier and Sarah Williams and Dirk Schadendorf and Axel Hauschild",
year = "2017",
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T1 - Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma

T2 - Final update of the pivotal ERIVANCE BCC study

AU - and for the ERIVANCE BCC Investigators

AU - Sekulic, Aleksandar D

AU - Migden, Michael R.

AU - Basset-Seguin, Nicole

AU - Garbe, Claus

AU - Gesierich, Anja

AU - Lao, Christopher D.

AU - Miller, Chris

AU - Mortier, Laurent

AU - Murrell, Dedee F.

AU - Hamid, Omid

AU - Quevedo, Jorge F.

AU - Hou, Jeannie

AU - McKenna, Edward

AU - Dimier, Natalie

AU - Williams, Sarah

AU - Schadendorf, Dirk

AU - Hauschild, Axel

PY - 2017/5/16

Y1 - 2017/5/16

N2 - Background: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. Methods: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. Results: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib. Conclusions: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. Trial registration: This study was registered prospectively with Clinicaltrials.gov , number NCT00833417on January 30, 2009.

AB - Background: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. Methods: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. Results: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib. Conclusions: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. Trial registration: This study was registered prospectively with Clinicaltrials.gov , number NCT00833417on January 30, 2009.

KW - Basal cell carcinoma (BCC)

KW - Efficacy

KW - Long-term

KW - Safety

KW - Vismodegib

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DO - 10.1186/s12885-017-3286-5

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