Megan May, PharmD, BCOP, and Daneng Li, MD, review the efficacy and the pivotal trials for the somatostatin analogues in the treatment of NETs.
Daneng Li, MD: I would like to start with the somatostatin analogues [SSAs] because, as we mentioned before, the somatostatin analogues are really the fundamental backbone of our treatment for our patients with neuroendocrine tumors. Megan, can you walk us through some of the efficacy and indications for the use of the somatostatin analogue therapies, particularly with the 2 long-acting somatostatin analogues, octreotide and lanreotide?
Megan May, PharmD, BCOP: Sure. I would be glad to. To start, what is the mechanism of these drugs, and why are we using them in this disease state? Most of our neuroendocrine tumors overexpress the receptors for somatostatin, which is a peptide hormone generated by the hypothalamus and blocks the release of growth hormones. The inhibition of the secretion of several hormones that include growth hormones, gastrin, and the vasoactive intestinal peptide are all affected.
The native somatostatin in our body rapidly degrades. So we have developed synthetic SSAs, which are more stable, to harness the therapeutic utility of somatostatins. They regulate those hormones that are related to the symptoms and tumor growth. That is why we are using these in the management of neuroendocrine tumors.
You mentioned the pivotal trials for each of these. There were 2 prospective, phase 3 pivotal randomized trails that evaluated the long-acting SSAs. The first was the PROMID trial, and this evaluated octreotide, the long-acting release [LAR]. It was found to significantly improve progression-free survival when compared with the placebo. This was in patients with locally inoperable or metastatic midgut neuroendocrine tumors. The median time to tumor progression was about 14 months in the octreotide-LAR arm compared with 6 months in the placebo arm.
After a long-term follow-up with the study, the median overall survival was not significantly different between the 2 arms of the octreotide-LAR and the placebo arms.
The other prominent trial is the CLARINET trial, and this evaluated lanreotide. The results did show that lanreotide was associated with significantly prolonged time to progression among patients who had locally advanced or metastatic nonfunctioning pancreatic or intestinal neuroendocrine tumors. Looking at the open label, the planned interim analysis of the lanreotide arm showed a progression-free survival of about 33 months.
When I was talking about the progression-free survival in each of those studies, they were different. How do you explain that? Well, the patients who they enrolled in the studies are a little different. In the CLARINET trial, most of the patients had already experienced stable disease for 3 to 6 months prior to randomization. That can explain why the progression-free survival was longer with the lanreotide in that study.