WEEKLY IMPORTANT NEWS FROM MEDSCAPE AND OTHER SOURCES
Τετάρτη, 25 Νοεμβρίου 2015
NO BENEFIT OF VISMODEGIB FOR PANCREATIC CANCER
In a phase II study reported in the Journal of Clinical Oncology, Catenacci et al found no benefit of adding vismodegib (Erivedge) to gemcitabine in patients with metastatic pancreatic cancer. Sonic hedgehog (SHH), an activating ligand of the smoothened receptor (SMO) inhibited by vismodegib, has been reported to be overexpressed in > 70% of pancreatic cancers.
In the double-blind study, 106 patients with disease not amenable to curative therapy who had received no prior therapy for metastatic disease received vismodegib plus gemcitabine (n = 53) or gemcitabine plus placebo (n = 53). The primary endpoint was progression-free survival. Exploratory correlative studies included serial serum SHH levels and contrast perfusion computed tomography imaging.
Median progression-free survival was 4.0 months in the combination group vs 2.5 months in the gemcitabine group (adjusted hazard ratio [HR] = 0.81, P = .30). Median overall survival was 6.9 vs 6.1 months (adjusted HR = 1.04, P = .84). Response was observed in 8% (all partial) vs 13% (complete 2%, partial 11%) of patients (P = .53). There were no significant associations between correlative markers and overall response rate, progression-free survival, or overall survival.
Preclinical studies to investigate mechanisms of SMO inhibition in two mouse pancreatic cancer models showed no significant differences with vismodegib in gemcitabine tumor delivery, tumor growth rate, or overall survival in either model.
The investigators concluded: “The addition of vismodegib to gemcitabine in an unselected cohort did not improve overall response rate, [progression-free survival], or [overall survival] in patients with metastatic [pancreatic cancer]. Our preclinical and clinical results revealed no statistically significant differences with respect to drug delivery or treatment efficacy using vismodegib.”
The study was supported by a National Cancer Institute grant.
Daniel V. T. Catenacci, MD, of the University of Chicago, is the corresponding author of the Journal of Clinical Oncology article.