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| |  Everolimus and Octreotide Combination Shows Promise for Neuroendocrine Tumours: Presented at ENETS By Karen Dente, MD BERLIN -- March 17, 2010 -- Investigators presented the rationale for combining several agents acting against various cellular targets in the treatment of neuroendocrine tumours (NETs), including the combination of everolimus and octreotide, at the 7th European Neuroendocrine Tumor Society Conference (ENETS). “Advanced neuroendocrine tumours are aggressive and incurable with standard treatment,” according to the study authors. Therefore, other cellular targets are being evaluated for this patient population. Researchers from Uppsala University Hospital, Uppsala, Sweden, and the University of Texas M. D. Anderson Cancer Center, Houston, Texas, reviewed the results of several phase 2 and 3 clinical trials including the RADIANT studies and the PROMID studies. In the phase 3 PROMID study, octreotide long-acting release (LAR) demonstrated significant antitumour effects against advanced midgut NETs. Other cellular targets being evaluated in the patient population with NETs include the mammalian target of rapamycin (mTOR), a kinase that is the central regulator of several signalling pathways related to cell growth, angiogenesis, and bioenergetics. “Because mTOR serves as a neoplastic switch activated by many cancer-related mutations, mTOR inhibition may have broad efficacy across tumour types, including neuroendocrine tumours. Targeting multiple pathways has thus emerged as a potent strategy for enhancing tumour control,” according to the researchers. One of several classes of mTOR inhibitors is everolimus. According to the results of the phase 2, nonrandomised RADIANT-1 study in patients with advanced pancreatic NETs who progressed during or after chemotherapy, median progression-free survival with everolimus was 9.7 months and 16.7 months when everolimus was combined with octreotide LAR. “Combination therapy with everolimus and octreotide offers promise in the treatment of advanced NETs,” the study authors concluded. Conducting phase 3 trials in patients with NETs has proven to be challenging due to the low incidence of the disease (about 5 per 100,000) in addition to its heterogeneity, and recruiting large enough patient populations remains challenging, although the incidence of NETs has steadily increased nearly 5-fold between 1973 and 2004. [Presentation title: Rationale for Combining mTOR With Other Targeted Agents in the Treatment of Neuroendocrine Tumors. Abstract C72]
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