Jonathan Strosberg, MD
Treatment advances for patients with neuroendocrine tumors (NETs) are bringing hope to a therapeutic landscape that has seen little activity until recent years, says Jonathan Strosberg, MD.
In an interview with OncLive
, Strosberg, medical oncologist, Department of Gastrointestinal Oncology, section head, Neuroendocrine Division, chair, Gastrointestinal Department Research Program, Moffitt Cancer Center, discussed recent developments and emerging agents in the field of NETs.
OncLive: What does the current treatment landscape for NETs look like?
There have been substantial changes over the last decade—we have actually had 9 phase III clinical trials in the NET field, 7 of which have met their primary endpoint. This is against a backdrop of really no phase II trials until the 2000s. So, it has been an exciting decade to treat NETs.
We have been talking about trial results that have been reported in the last several years; these include the NETTER-1 study, which randomized patients to receive Lutathera with octreotide in patients with progressive midgut NETs. There is also the TELESTAR trial, which randomized patients with diarrhea related to carcinoid syndrome to receive telotristat (Xermelo) versus placebo and showed a significant improvement in diarrhea as well as reduction in urine 5-HIAA. Then there are the RADIANT trials, which prove the role of everolimus (Afinitor) in both pancreatic and non-pancreatic neuroendocrine tumors.
Are there any significant ongoing trials?
As far as currently accruing clinical trials, I think there are several that are interesting. One is ECOG 2211, which is looking at temozolomide plus capecitabine versus temozolomide monotherapy in patients with progressive pancreatic NETs. It is a very exciting trial because there have been a lot of small retrospective studies, a few prospective studies looking at temozolomide-based combinations, but very little in terms of robust prospective clinical trials. This is going to be very important to help figure out if combinations are better than monotherapy.
We are looking forward to the results of pazopanib versus placebo in non-pancreatic NETs; if positive, this will be this first angiogenesis inhibitor to be used outside of pancreatic NETs—in other words, in carcinoid tumors.
There is an interesting trial that has not yet completed accrual that is looking at streptozocin chemotherapy versus everolimus in patients with pancreatic NETs, which is trying to get at the whole sequencing question.
And then there are some trials that are just starting out that are looking at immunotherapy, which really has not been well investigated in this field.
What is the biggest challenge in treating neuroendocrine tumors?
Neuroendocrine tumors are extremely diverse. The first thing to figure out is which segment you are dealing with. We can categorize them in many different ways based on where they originate, their differentiation, grade, whether they are growing quickly or slowly, whether they are liver predominant or not, whether they express metastin receptors—so it is important to get all of the baseline clinical characteristics fully understood before coming up with a treatment plan.
We are learning more about the biology of the disease; mutations still do not have a lot of therapeutic implications, but that'll probably change.
How do you see the field progressing in the next 5 to 10 years?
I think the most important trials are going to hopefully help us figure out how to best sequence treatments. Right now, there are a bunch of emerging therapies but really no information on how best to sequence them. These sequencing studies are just the start—perhaps they will give us some more information on how we should start sequencing treatments in the general population.