Vismodegib, a Hedgehog pathway inhibitor (HPI), in advanced basal cell carcinoma (aBCC): STEVIE study interim analysis in 300 patients.

Abstract

9036 Background: Therapy options are limited for locally advanced (la) and metastatic (m) BCC. Aberrant Hedgehog (Hh) signaling is the key driver in BCC pathogenesis. Vismodegib, a first-in-class HPI, is approved in the US for use in adults with aBCC. STEVIE is an ongoing study focusing on safety of vismodegib therapy in patients with aBCC. We present data from the third interim analysis (data cutoff: 19 October 2012), which also permits a preliminary assessment of efficacy of vismodegib in the largest study ever conducted in patients with aBCC. Methods: Adult patients with laBCC or mBCC received oral vismodegib 150 mg QD until progressive disease, unacceptable toxicity, or withdrawal. Safety is the primary objective of STEVIE (Common Terminology Criteria for Adverse Events 4.0). Secondary endpoints include efficacy variables. Recruitment is ongoing. Results: This analysis included 300 patients with locally advanced (n=278) or metastatic (n=22) BCC from 11 countries with potential for ≥3-month follow-up. Median treatment duration, including vismodegib interruption, was 176.5 days (range 1-455 days). Common treatment-emergent AEs (TEAEs), typically ≤ grade 2, included muscle spasm (59.3%), alopecia (49.3%), and dysgeusia (41.0%) and were comparable to prior analysis. Serious TEAEs occurred in 53 patients (17.7%). 131 (43.7%) discontinued from the study, mainly due to patient or investigator request (n=41), AEs (n=35), disease progression (n=18) or death (n=13; 7 due to AEs assessed by the investigator as unrelated to study drug, 3 due to AEs not possible to be assessed, 3 due to disease progression). Preliminary best overall response in patients with available tumor assessments (n=251) included complete response (17.5%), partial response (39.8%), stable disease (39.0%) and progressive disease (2.8%). Patient recruitment and monitoring is ongoing. Conclusions: This third interim analysis of STEVIE confirms the previously observed vismodegib safety profile but can also provide further information about the high rate of tumor control with vismodegib in a large series of patients with aBCC. Clinical trial information: 2011-000195-34.