Somatostatin Analogs and PRRT: Treatment Considerations
Panelists: Simron Singh, MD, Odette Cancer Centre; Jonathan R. Strosberg, MD Moffitt Cancer Center
Simron Singh, MD: As PRRT’s use becomes more widespread, I think there is still a lot of confusion about what the role of somatostatin analogs is concurrently as well as for maintenance after PRRT. Based on your experience, do you want to tell us what you do? What questions do you think remain to be answered about the concurrent use of these cold or hot analogs?
Jonathan R. Strosberg, MD: That’s a good question. The first question is whether somatostatin analogs have a negative or a positive impact on PRRT. We really don’t know. Traditionally, long-acting somatostatin analogs were held 6 weeks before each PRRT cycle in most single-arm studies as well as on the NETTER-1 study. This was based on the assumption that they may compete for occupying the somatostatin receptor. But what we found with imaging is that somatostatin analogs, even given shortly before gallium-68 or octreoscan [octreotide scan], don’t really reduce tumoral uptake of the radiotracer. What that suggests is you could probably give somatostatin analogs relatively shortly before each PRRT treatment without impacting efficacy. So the answer to that is: We really don’t know.
On the NETTER-1 study, all patients continued octreotide during and after treatment. We don’t know how many patients on the trial had carcinoid syndrome, but, presumably, we expect that a lot of them had it. So that was a strategy taken on the NETTER-1 study. I would say that for patients with functional tumors, you certainly want to continue the somatostatin analog during treatment as well as after. What we tend to do is time the treatment so that it’s 4 weeks after the somatostatin analog. Then we give a somatostatin analog right after Lutathera [lutetium-177 dotatate], and then 4 weeks later, and sort of continue. The FDA approval says that it can be given 4 weeks before each Lutathera dose.
For patients with nonfunctioning tumors, I think there’s a huge amount of controversy as to whether to continue the somatostatin analog during and after treatment. If patients have progressed relatively slowly on the somatostatin analog, we’ll sometimes just give a shot after each Lutathera treatment, skip the in-between shot, and then continue. If they progress relatively quickly on a somatostatin analog, we’ll stop the drug altogether. There is some nonrandomized data that suggests that continuing a somatostatin analog is associated with better outcomes, but nonrandomized data is subject to a huge amount of selection bias. And so, I’m a bit skeptical of that nonrandomized data. We should be considering a randomized trial.
Simron Singh, MD: So this is something we still need to sort of fine-tune in our treatment with PRRT?
Jonathan R. Strosberg, MD: It’s not just PRRT. The whole question of using a somatostatin analog beyond progression is one that exists not only for PRRT but for every second-line treatment. When a patient progresses on a somatostatin analog and you start everolimus, for example, do you typically continue the somatostatin analog or do you stop it?
Simron Singh, MD: That’s a really good question. I don’t know if I know the right answer. We do know that with everolimus and octreotide there is probably some synergy in their mechanisms of action. So in certain situations I definitely would consider continuing it, realizing that they also have some overlapping toxicity, unfortunately. I want to monitor things like hyperglycemia, etcetera, closely. But you’re right. It’s one of those questions that we don’t know the answer to. We also wonder if we’re really dealing with a heterogeneous population. We might be using everolimus to deal with some of that population, for example, and the somatostatin analogs may be keeping some of the other population a bit quieter.