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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• 作者：Reinhard Dummer ; MD^a ; ^{reinhard.dummer@usz.ch" class="auth_mail" title="E-mail the corresponding author} ; Alexander Guminski ; MD ; PhD^b ; Ralf Gutzmer ; MD^c ; Luc Dirix ; MD^d ; Karl D. Lewis ; MD^e ; Patrick Combemale ; MD^f ; Robert M. Herd ; MD^g ; Martin Kaatz ; MD^h ; ⁱ ; Carmen Loquai ; MD^j ; Alexander J. Stratigos ; MD^k ; Hans-Joachim Schulze ; MD^l ; Ruth Plummer ; MD^m ; Sven Gogov ; MDⁿ ; Celine Pallaud ; PhDⁿ ; Tingting Yi ; PhD^o ; Manisha Mone ; PhD^o ; Anne Lynn S. Chang ; MD^p ; Frank Corné ; lis ; MD^q ; Ragini Kudchadkar ; MD^r ; Uwe Trefzer ; MD^s ; John T. Lear ; MD^t ; Dalila Sellami ; MD^o ; Michael R. Migden ; MD^u
• 关键词：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
• 刊名：Journal of the American Academy of Dermatology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：75
• 期：1
• 页码：113-125.e5
• 全文大小：2899 K

文摘

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.