Treatment Strategies in Neuroendocrine Tumors - Episode 5

Overview of Somatostatin Analogs for NETs


Timothy J. Hobday, MD: Somatostatin analogs are currently used for 2 different purposes in our patients. One is to control the hormones that are produced by their tumor that are causing them troubles—whether it’s serotonin, the carcinoid syndrome, or a myriad of other hormones that can be produced by neuroendocrine tumors.

The second reason to treat patients with somatostatin analogs is to try to slow or stop the progression, the slow growth, of their disease. This has been demonstrated in 2 randomized trials, one for octreotide and one for lanreotide, in slightly different populations. This has actually been known for 30 or 40 years, but it was not demonstrated in clinical trials until recently. Actual reduction in tumor bulk, or tumor volume, is quite rare. About 1% or 2% of patients have their tumor shrink. But in a patient where the tumor is slowly growing, stability and halting that growth for a period of time is one of the goals of somatostatin analog therapy.

Jonathan R. Strosberg, MD: There are 2 commercially available somatostatin analogs in gastroenteropancreatic neuroendocrine tumors—octreotide (Sandostatin) and lanreotide (Somatuline). Sandostatin is an intramuscular injection that is typically administered at a dose of 30 mg every 4 weeks. That’s sort of the standard dose of the drug. Somatuline is a deep subcutaneous injection. The standard dose is 120 mg every 4 weeks.

They’re both very similar drugs. They target the somatostatin receptor. They most avidly target somatostatin receptor subtype 2. The pharmacodynamic profile is extremely similar. The clinical data are quite similar, as far as control of hormonal symptoms—there have been studies showing that they’re fairly interchangeable—and control of tumor growth. Each of them has had a phase III study showing inhibition of tumor growth, the PROMID study for Sandostatin and the CLARINET study for Somatuline.

If you look at the hazard ratio for midgut neuroendocrine tumors in both studies, it was quite similar. So, we think that the drugs work very similarly. There probably is not a big difference in efficacy between the 2 drugs. The FDA labeling is slightly different. Sandostatin is only formally indicated for symptom control, control of the carcinoid syndrome, despite the fact that the PROMID study also showed tumor control. Somatuline has an indication for tumor control in gastroenteropancreatic neuroendocrine tumors for inhibition for tumor growth. It also recently received an approval for control of carcinoid syndrome. So, its formal indication is broader than that of Sandostatin.

Heloisa P. Soares, MD: Somatostatin analogs have been around for a very long time. Initially, one of the first papers that was published was about the use of octreotide, short acting, in the control of carcinoid syndrome. That has proven that it will improve flushing, diarrhea, and even decrease urinary 5-HIAA, which is a biomarker for carcinoid syndrome—if I may put it in that way. Then, later, there was the development of long-acting octreotide. There was a large trial done comparing it to placebo. The trial showed that patients that received octreotide, long acting at 30 mg intramuscular every 4 weeks, had improvements in tumor control and symptoms. Most recently, lanreotide, which is provided by a different company, also showed, in the CLARINET study, that you can have improvements in progression-free survival versus placebo.

So, we now have 2 long-acting medications, from different companies, that can help to delay tumor progression, or progression-free survival, and also control symptoms of carcinoid syndrome in the patients that have that.

Transcript Edited for Clarity