Original article
The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma

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Background

The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.

Objective

This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.

Methods

In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.

Results

Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively).

Limitations

No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved.

Conclusion

With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC.

Key words

advanced basal cell carcinoma
Basal Cell Carcinoma Outcomes with LDE225 Treatment study
hedgehog pathway inhibitor
locally advanced basal cell carcinoma
metastatic basal cell carcinoma
sonidegib

Abbreviations used

BCC
basal cell carcinoma
BOLT
Basal Cell Carcinoma Outcomes with LDE225 Treatment
HPI
hedgehog pathway inhibitor
laBCC
locally advanced basal cell carcinoma
mBCC
metastatic basal cell carcinoma
mRECIST
modified Response Evaluation Criteria in Solid Tumors
ORR
objective response rate
RECIST
Response Evaluation Criteria in Solid Tumors
WHO
World Health Organization

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Funded by Novartis Pharmaceutical Corp. Medical editorial assistance was provided by Christopher Reina and Jillian Brechbiel (Articulate Science, Hamilton, NJ). Financial support for editorial assistance was provided by Novartis Pharmaceuticals Corp.

Disclosure: Dr Dummer acted as a consultant for and received research funding/fees from Novartis, Bristol-Myers Squibb, Roche, and GlaxoSmithKline, and acted as a consultant for Merck Sharp & Dohme and Amgen. Dr Guminski acted as a speaker for, participated in an advisory board for, and received honoraria from Novartis. Dr Gutzmer received a research grant paid to the institution from Roche Pharma, Novartis, Johnson & Johnson, and Pfizer; received honoraria for lectures from Roche, Bristol-Myers Squibb, Merck Sharpe & Dohme, GlaxoSmithKline, Novartis, Merck Serono, Almirall, LEO Pharma, Amgen, Galderma, and Boehringer Ingelheim; and participated in an advisory board for and received honoraria from Roche, Bristol-Myers Squibb, Merck Sharpe & Dohme, GlaxoSmithKline, Novartis, Almirall, LEO Pharma, Amgen, and Pfizer. Drs Dirix and Lear participated in an advisory board for and received honoraria from Novartis. Dr Lewis received research funding paid to the institution from Novartis. Dr Herd is a principal investigator for and received honoraria from Novartis. Dr Kaatz is a primary investigator for, participated in an advisory board for, and received honoraria from Roche Pharma, Merck Sharpe & Dohme, Novartis, Bristol-Myers Squibb, and Janssen. Dr Loquai acted as a speaker for, participated in an advisory board for, and received honoraria from Bristol-Myers Squibb, Roche, Novartis, and Merck Sharpe & Dohme. Dr Stratigos acted as a speaker for, participated in an advisory board for, and received honoraria from Roche; participated in an advisory board for, received honoraria from, is a primary investigator for, and received research funding from Novartis; and acted as a speaker for, received honoraria from, is a primary investigator for, and received a research grant from LEO Pharma. Dr Schulze is a principal investigator for Novartis and received honoraria from Novartis paid to the institution. Drs Gogov, Yi, Mone, and Sellami are employed by Novartis and own stock. Dr Pallaud is employed by Novartis. Dr Chang is a primary investigator for, received a research grant/funding paid to the institution from, participated in an advisory board for, and received honoraria from Novartis. Dr Kudchadkar participated in an advisory board for and received honoraria from Bristol-Myers Squibb and Genentech. Dr Trefzer acted as an advisor for and received honoraria from Hofmann-La Roche; participated in an advisory board for and received honoraria from Merck Sharpe & Dohme; and acted as a speaker and received honoraria from Novartis. Dr Migden participated in an advisory board and received honoraria from Genentech, Novartis, and Eli Lilly. Drs Combemale, Plummer, and Cornélis have no conflicts of interest to declare.

This work was presented in part at the 2014 Annual Meeting of the European Society for Medical Oncology, Madrid, Spain, September 26-30, 2014; 23rd Annual European Academy of Dermatology and Venereology, Amsterdam, The Netherlands, October 8-12, 2014; 3rd World Cutaneous Malignancies Congress, San Francisco, CA, October 29-31, 2014; 2014 Annual Meeting of the Society for Melanoma Research, Zurich, Switzerland, November 13-16, 2014; and 73rd Annual Meeting of the American Academy of Dermatology, San Francisco, CA, March 20-24, 2015.

Supplemental tables and figures are available at http://www.jaad.org.

© 2016 by the American Academy of Dermatology, Inc. Published by Elsevier, Inc.