The addition of vismodegib, a sonic hedgehog antagonist, to gemcitabine in an unselected cohort did not improve overall response rate, progression-free survival, or overall survival in patients’ metastatic pancreatic cancer, a new study published online ahead of print in the Journal of Clinical Oncology has shown.1

Because sonic hedgehog, an activating ligand of smoothened, is overexpressed in more than 70% of pancreatic cancers, researchers sought to evaluate the combination of vismodegib and gemcitabine compared with gemcitabine plus placebo in patients with metastatic pancreatic cancer.

For the multicenter phase 1b/2 study, researchers enrolled 106 patients with pancreatic cancer not amenable to curative therapy to the phase 2 portion.

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No patients had received prior therapy for metastatic disease and had a Karnofsky performance score of 80 or higher. Participants were randomly assigned 1:1 to receive gemcitabine plus vismodegib or placebo.

Results showed that median progression-free survival was 4.0 months (95% CI, 2.5 – 5.3) in the vismodegib arm and 2.5 months (95% CI, 1.9 – 3.8) in the placebo arm (HR, 0.81; 95% CI, 0.54 – 1.21; P = .30).

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Median overall survival was 6.9 months (95% CI, 5.8 – 8.0) and 6.1 months (95% CI, 5.0 – 8.0), respectively (HR, 1.04; 95% CI, 0.69 – 1.58; P = .84). Overall response rates were also no statistically different between the 2 treatment arms.

Vismodegib is currently approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic or recurrent locally advanced basal cell carcinoma that is not amenable to surgery or radiotherapy.


  1. Catenacci DVT, Junttila MR, Karrison T, et al. Randomized phase 1b/2 study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer [published online ahead of print November 2, 2015]. J Clin Oncol. doi: 10.1200/JCO.2015.62.8719.