Lanreotide Approval Opens Doors for Treatment of GEP-NETs

Alexandria Phan, MD

Lanreotide (Somatuline Depot), which was recently approved by the FDA, is the first and only anti-tumor therapy with a statistically significant progression-free survival benefit in the treatment of adults patients with gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs).

The approval was based on the CLARINET study, led by Alexandria Phan, MD, the director of GI Medical Oncology at Houston Methodist. In a recent interview with OncLive, Phan discusses the study’s objectives and the drug’s potential to significantly improve treatment options and quality of life for patients with advanced unresectable, metastatic GEP-NETs.

What were the objectives of the CLARINET study?

It was a pivotal study where we knew that whatever the result was it was going to change the paradigm of therapy for us. The study involved patients that had well-differentiated, neuroendocrine tumors of the intestinal track and the pancreas and they randomized all of those patients between placebos and lanreotide; the treatment arm. The study was actually a phase III, placebo control randomized study, so it was typical that any results coming from there are usually category one evidence for anything that will go into practice. The primary end point is progression-free survival, which is a robust outcome.

What were the study outcomes?

The study outcomes show that patients treated with lanreotide have improved progression-free survival compared to placebo, and a 53% reduction of risk of death after being treated with lanreotide. What is interesting is this study is a little bit different and pretty comprehensive. It involves everything in the intestinal track as well as the pancreas. Most studies actually break them up between pancreas and neuroendocrine tumor of the intestines. But this incorporated all of them.

What is the real-world impact lanreotide could have for treating patients with these unresectable, metastatic tumors?

Well-differentiated, neuroendocrine tumors are typically slow growing. They are never curable if they present with metastatic disease. The majority of patients, 70% of them, usually present with advanced disease because patients are going around and they are getting misdiagnosed multiple times, so by the time they present they have an advanced disease. This unfortunately presents as incurable disease. But fortunately, patients are typically not symptomatic so their quality of life is still very good. So the idea of trying to blast them with chemotherapy or anything that can make their quality of life worse is the worse way that you can approach treating this patient.

Looking for therapy that actually sustains or maintains their quality of life and improves the progression-free survival and overall survival ultimately is the goal. That is what the CLARINET study was about-- to look and see if you can lengthen that progressive-free period while also maintaining their quality of life. It is not intended to look for size reduction in a typical chemotherapy way. But there were more patients with responding disease, meaning tumor shrinkage, than those who were treated on the placebo. This makes sense because any therapy that is going to lengthen the progressive-free interval is going to have some tumor shrinkage. But the tumor shrinkage is not what we are looking for in an indolent disease. We are looking for prolonged life interval.

Now that lanreotide is approved how do you see the drug being incorporated into the treatment process for these patients?

I am very proud to be involved in this study because any study that gives patients with incurable disease another option that is tolerable, can sustain their quality of life, and potentially prolong their overall survival. And in this case, improving their progression-free survival on a statistically significant level is stellar. So I think what I take home from the results of this study and the drug being FDA approved is that all patients with well-differentiated, neuroendocrine tumors of the pancreas or the GI track now have another option and that is an option that is actually safe and very well tolerated. Their quality of life can be sustained and not worsen because of their treatment.

Are there any significant side effects associated with this drug?

The side effects are very similar to what we already know about this drug. It is a biological; it is in a sense a synthetic somatostatin analog. Somatostatin analogs have been used in this country and in Europe to treat other endocrine disease and to treat GI bleeding, and the side effects are very, very minimal. It is not chemotherapy, so it doesn’t have those harsh side effects. There is no immunosuppression that you typically see, no hair loss, none of those gruesome things patients think of when they hear cancer therapy.

Is there a certain patient that would benefit the most from this drug?

For oncologists, matching the goal of their therapy with the risk the patients and oncologist are comfortable is key. I think anybody that has a disease that is advanced, unresectable, a typical indolent disease, this would be a good option for him or her, especially for those who have the pancreatic or GI track neuroendocrine tumors. There are other options for pancreatic or GI track neuroendocrine tumor treatment as well, but those have more side effects in my opinion than this drug.

It sounds like the drug has a lot of great potential

It is really exciting. When you go into a study you are always thinking ‘who knows if we will have the result in my lifetime?’ It is nice to have the results now, and have the result be something that will change the paradigm of therapy.

Absolutely. You mentioned that many patients that have these pancreatic or GI track neuroendocrine tumors aren’t diagnosed until the disease is advanced. Is there anything that can be done to diagnose this disease in an earlier stage?

Anything that is rare, you need to improve awareness of it and that will improve detection. The incidence of neuroendocrine tumors is on the rise because we have better diagnostic tools to pick them up. But I think because the symptoms are so vague and so common with many other issues, if people are not aware of this disease they aren’t going to look for it. This is something that can be the cause of diarrhea for example. That is often on the primary care physicians to identify because by the time anyone comes to an oncologist the disease is often advanced.

For oncologists, having awareness of this cancer and really being aware of treatment options and the whole therapy and side effect profile is key in making the right decisions for patients. Having more choice actually improves the quality of life for the oncologist even more because instead of scratching their head trying to refer patients or trying to find clinical trials they have this option. That helps the oncologist’s quality of life so they don’t lose so much sleep. More oncologists being aware of this drug as an option is really the key.