A phase II, randomized, placebo-controlled study of vismodegib as maintenance therapy in patients with ovarian cancer in second or third complete remission Journal Article


Authors: Kaye, S. B.; Fehrenbacher, L.; Holloway, R.; Amit, A.; Karlan, B.; Slomovitz, B.; Sabbatini, P.; Fu, L.; Yauch, R. L.; Chang, I.; Reddy, J. C.
Article Title: A phase II, randomized, placebo-controlled study of vismodegib as maintenance therapy in patients with ovarian cancer in second or third complete remission
Abstract: Purpose: Hedgehog pathway inhibition has been suggested as a potential maintenance treatment approach in ovarian cancer through disruption of tumor-stromal interactions. Vismodegib is an orally available Hedgehog pathway inhibitor with clinical activity in advanced basal cell carcinoma and medulloblastoma. This phase II, randomized, double-blind, placebo-controlled trial was designed to provide a preliminary estimate of efficacy in patients with ovarian cancer in second or third complete remission (CR). Experimental Design: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in second or third CR were randomized 1:1 to vismodegib (GDC-0449; 150 mg daily) or placebo three to 14 weeks after completing chemotherapy. Treatment continued until radiographic progression or toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results: One hundred four patients were randomized to vismodegib (n = 52) or placebo (n = 52); median PFS was 7.5 months and 5.8 months, respectively [HR 0.79; 95% confidence interval (CI), 0.46- 1.35]. The HR was 0.66 (95% CI, 0.36-1.20) for second CR patients (n=84) and 1.79 (95% CI, 0.50-6.48) for third CR patients (n = 20). The most common adverse events in the vismodegib arm were dysgeusia/ ageusia, muscle spasms, and alopecia. Grade 3/4 adverse events occurred in 12 patients (23.1%) with vismodegib and six (11.5%) with placebo. Hedgehog expression was detected in 13.5% of archival tissues. Conclusions: In this study, the sought magnitude of increase in PFS was not achieved for vismodegib maintenance versus placebo in patients with ovarian cancer in second or third CR. The frequency of Hedgehog ligand expression was lower than expected. ©2012 AACR.
Journal Title: Clinical Cancer Research
Volume: 18
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2012-12-01
Start Page: 6509
End Page: 6518
Language: English
DOI: 10.1158/1078-0432.ccr-12-1796
PROVIDER: scopus
PUBMED: 23032746
DOI/URL:
Notes: --- - "Export Date: 2 January 2013" - "CODEN: CCREF" - "Source: Scopus"
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  1. Paul J Sabbatini
    199 Sabbatini