New and Upcoming Options for Neuroendocrine Tumors

Arvind Dasari, MD, MD Anderson Cancer Center, Houston, TX, reviews the presentation he gave at the 2023 Great Debates and Updates in Gastrointestinal Malignancies meeting, on the evolving treatment landscape for neuroendocrine tumors. Dr Dasari covers the ongoing trials investigating targeted agents and peptide receptor radionuclide therapy.

Transcript:

Hello, I'm Arvind Dasari. I'm an associate professor in the Department of GI Medical Oncology at MD Anderson Cancer Center and I'm here in Chicago at Great Debates in GI Malignancies. Today we talked about neuroendocrine tumors and the recent updates and how the treatment landscape in particular is evolving for these tumors. In addition to the drugs that have already been approved—somatostatin analogs (SSAs) such as octreotide and lanreotide and also small molecule tyrosine kinase inhibitors such as sunitinib and everolimus—we also have PRRT, which is peptide receptor radionuclide therapy, which is FDA-approved as well for neuroendocrine tumors. There's a lot of work that's going on and really exciting about the pace of change and all the research that's going on. That is what we discussed at this meeting.

In particular with regards to the targeted agents, there is a large phase 3 trial that's ongoing of cabozantinib. This is the CABINET trial, evaluating the activity of cabozantinib versus placebo in patients with well differentiated gastroenteropancreatic neuroendocrine tumors who are being enrolled onto 1 of 2 cohorts, either carcinoid tumors or pancreatic neuroendocrine tumors with a primary endpoint of progression-free survival. And this trial is actively enrolling and we're hoping to see the results soon.

With regards to peptide receptor radionuclide therapy, the current FDA-approved option is Lutathera, which is lutetium-177 based PRRT. The ongoing efforts in this space building on the success that we've seen with NETTER-1 trial include expanding the indication of PRRT. In the NETTER-1 trial, there were only small bowel neuroendocrine tumors that were enrolled, in patients who had progressive disease with prior SSAs. The NETTER-2 trial that has finished enrollment is evaluating the activity of PRRT in a broader patient population, all gastroentropancreatic neuroendocrine tumors, and also with a higher Ki-67 of 15% to 55%. Patients are randomized to either PRRT or octreotide. And this trial has finished enrollment and we're awaiting the results of this trial.

There are a couple of other trials, such as COMPETE and COMPOSE, that although they do have a lutetium-177 radioactive ligand, they have changed the peptide ligand that binds to the somatostatin receptors. Early data suggests that perhaps that this could have better pharmacokinetics and perhaps more response. And there are 2 trials that are ongoing, in the first- and second-line setting, evaluating this form of PRRT against standard-of-care therapies.

Lutetium-177 is the radioactive ligand in all the trials that we've discussed so far. This is a beta emitter. Now there there's some excitement around alpha emitters and the advantage is that we may have better efficacy with alpha emitters and with less toxicity. And there are several alpha that are being evaluated, including actinium-225, lead-212, and bismuth-based radioactive ligands. The actinium compound is being evaluated in an ongoing phase 1b trial that is enrolling patients as well. And again, this is a really exciting development and it'll be interesting to see what the activity of this therapy will be. As a note, this trial is enrolling patients who previously received lutetium-177.

Finally, in the same space of patients who were previously treated, there is the NET-RETREAT trial, which is specifically asking the question, for patients who have received lutetium-177-based PRRT before, and have had benefit, could we re-treat them with the same treatment? And this is a Cooperative Group trial that will randomize patients who previously received PRRT and had clinical benefit defined as at least 12 months of stable disease post-completion of the last dose of PRRT. And they're randomized to re-treatment with PRRT versus standard-of-care everolimus. And this trial should start enrolling soon.

Overall, I think we've seen a lot of success in improving outcomes for patients with neuroendocrine tumors and all these trials that we touched upon today, I think will only further improve options for patients and help them live longer with therapies that are better tolerated and with fewer side effects. So very excited about the future.

Source:

Dasari A. “Advances in Neuroendocrine Tumors (NETs).” Presented at Great Debates and Updates in Gastrointestinal Malignancies; March 30-April 1, 2023; Chicago, IL.