1112PD - Efficacy and Safety of the Hedgehog Pathway Inhibitor Vismodegib in Patients with Advanced Basal Cell Carcinoma (BCC): 12-Month Erivance BCC Study Update

Abstract

ABSTRACT Background Vismodegib (Erivedge™, GDC-0449) is a first-in-class small-molecule inhibitor of the Hedgehog signaling pathway, which is implicated in the pathogenesis of BCC. ERIVANCE BCC is the pivotal trial of vismodegib for treatment of locally advanced (laBCC) and metastatic BCC (mBCC) patients (pts) for whom there are no other effective therapies. The study met its primary endpoint of overall response rate by independent review (Dirix, ESMO 2011 LBA#1). On behalf of the ERIVANCE BCC investigators, we present the previously unreported updated investigator-assessed (I-A) efficacy and safety endpoints as of Nov 28, 2011 (additional 12 months of follow-up). Methods In this multicenter, nonrandomized 2-cohort study, pts with histologically confirmed laBCC (deemed inoperable or for whom surgery would be significantly disfiguring) or mBCC with RECIST-measurable disease, received 150 mg oral vismodegib daily. Results 104 pts (71 laBCC/33 mBCC) enrolled at 31 global sites. I-A efficacy endpoints were: Nov 26, 2010 Data Cut Nov 28, 2011 Data Cut Parameter mBCC (n = 33) laBCC (n = 63) mBCC (n = 33) laBCC (n = 63) Overall Response Rate (ORR), n (%) [95% CI] 15 (45.5) [28.1–62.2] 38 (60.3) [47.2–71.7] 16 (48.5) [30.8–66.2] 38 (60.3) [47.2–71.7] Median Duration of Response (DOR), months [95% CI] (n = 15) 12.9 [5.6–12.9] (n = 38) 7.6 [7.4–NE] (n = 16) 14.7 [5.6–NE] (n = 38) NE [9.0–NE] Median Progression-free Survival (PFS), months [95% CI] 9.2 [7.4–NE] 11.3 [9.5–16.8] 9.3 [7.4–16.6] 12.9 [10.2–NE] Median Overall Survival (OS), months [95% CI] NA NA 24.1 [14.3–NE] NE [NE–NE] With a median follow-up of 22.3 months, 1- and 2-year survival rates were 78% (95% CI 63.6–92.4%) and 60% (95% CI 42.6–78.1%), for mBCC and 93.1% (95% CI 86.6–99.6%) and 85% (95% CI 75.6–94.7%), for laBCC. Adverse events (AEs) in >30% of pts were muscle spasms, alopecia, dysgeusia, weight decrease, fatigue, nausea, and amenorrhea (in 2/6 female nonmenopausal pts). Serious AEs were reported in 33 pts (32%), compared with 26 (25%) in Nov 2010. Conclusions This 12-month update of I-A efficacy and safety data from the ERIVANCE BCC study confirms the significant clinical benefit of vismodegib in laBCC and mBCC reported at primary analysis. Median DOR and PFS increased numerically with further follow-up. The AE profile was consistent with the prior data cut. Following approval of vismodegib by the FDA, these data further support vismodegib as an effective treatment option for pts with advanced BCC. Disclosure A. Sekulic: Speaker bureau: Genentech/Roche. M.R. Migden: Advisory board: Genentech. A. Oro: Grant: Genentech, Novartis, Infinity. K. Lewis: Grant: Genentech Consulting fee/honoria: Genentech. J. Hou: Employee: Genentech Shareholder: Genentech. H. Yue: Employee: Genentech Shareholder: Genentech. A. Hauschild: Consult/honoraria:Roche, AZ, Biovex, BMS, Boehringer-Ingelheim, Celgene, Eisai, GSK, IGEA, Merck/MSD, Novartis,SOBI Reviews:Roche Spker bureau:Roche, AZ, Biovex, BMS, Boehringer-Ingelheim, Celgene, Eisai, GSK, IGEA, Merck/MSD, Novartis,SOBI. All other authors have declared no conflicts of interest.