Long-Termsafety And Efficacy Of Vismodegib In Patients With Advanced Basal Cell Carcinoma: 30-Month Final Update Of The Pivotal Erivance Bcc Study

9013 Background: BCC pathogenesis involves abnormal Hedgehog pathway (HP) signaling. In the ERIVANCE BCC trial, vismodegib (VISMO), the first FDA-approved HP inhibitor (HPI), showed objective response rates (ORRs) by independent review of 30% in metastatic (m) BCC and 43% in locally advanced (la) BCC, with median duration of response (DOR) of 7.6 mo for both. ORRs by investigator (INV) review were 45% (mBCC) and 60% (laBCC), with median DOR of 12.9 and 7.6 mo, respectively. Some patients (pts) continued VISMO treatment >3 yrs after start of therapy. We present safety and INV-assessed efficacy results 30 mo (30 May 2013) after primary analysis (26 Nov 2010). Methods: ERIVANCE BCC was a multicenter, international, nonrandomized study in pts (N=104) with radiographically measurable mBCC or laBCC (surgery inappropriate due to multiple recurrence, or substantial morbidity or deformity anticipated) receiving oral VISMO 150 mg daily until disease progression or intolerable toxicity. Key secondary endpoints included INV-ORR, progression-free survival (PFS), DOR, overall survival (OS), and safety. Results: At data cutoff, 9 pts (9%) continued to undergo protocol-specified assessments and 69 pts (66%) were in survival follow-up. ORR (INV) was 48.5% (mBCC) and 60.3% (laBCC), comparable with primary analysis. Median DOR (INV) improved from 12.9 and 7.6 mo for mBCC and laBCC (primary analysis) to 14.8 and 26.2 mo, respectively. Median (95% CI) PFS was 9.3 (7.4-16.6) and 12.9 (10.2-28.0) mo in mBCC and laBCC, respectively; median OS for mBCC was 33.4 (18.1-not estimable) mo and not reached in laBCC. Adverse events (AEs) remained consistent with the primary analysis; >30% of pts reported muscle spasm, alopecia, dysgeusia, weight decrease, fatigue, and nausea. 23 (22.1%) pts reported AEs leading to treatment discontinuation. 17 deaths (mBCC=10; laBCC=7) have been reported since the primary analysis and were not considered drug related. 16 deaths occurred in survival follow-up; 1 pt died due to general deterioration of health. Conclusions: The 30-month ERIVANCE BCC update confirmed the efficacy of the primary analyses and showed long-term consistent safety of VISMO in pts with aBCC. Clinical trial information: NCT00833417.