Future Directions in the Management of Neuroendocrine Tumors

Diane Reidy-Lagunes, MD: There have been many studies in neuroendocrine cancers that have looked at the role for immunotherapy, in particular checkpoint inhibitors. Most of those studies haven’t panned out to be helpful in terms of improving progression-free survival or response rate. There are reports in studies of small response rates, but it hasn’t shown the promise that we wanted. There’s been a lot of emphasis in looking at poorly differentiated neuroendocrine carcinomas in high-grade neuroendocrine cancers to see if that patient population would be the most ideal. The reason for that is, those patients tend to have a higher mutational burden and may be more responsive to immunotherapies compared with our lower or intermediate-grade neuroendocrine cancers, where the mutational burden is generally very low.

Those trials are still ongoing. There’s 1 trial of combination of ipilimumab-nivolumab that did look like there was a positive response, but unfortunately, that study and subsequent studies haven’t been replicated. That the jury is still out on the role of immunotherapy with our disease. Importantly, as a result, since the checkpoint inhibitors by themselves haven’t been proven to be helpful, adding that on to therapies that we know already have promise and activity and could potentially result in a better outcome or better progression-free survival. That’s where the money will be. But by itself, unfortunately, we haven’t seen the results that wanted to date.

What’s exciting about neuroendocrine cancers is we were the first to have a targeted approach. Somatostatin analogues 30 years ago were a targeted approach. PRRT [peptide receptor radionuclide therapy], 177Lu-DOTA-TATE is a targeted approach to target the somatostatin receptor, and it works incredibly well. We’re all very excited about that, and we want to build on that. There are other opportunities and things in the pipeline to think about how we can improve the outcomes for our patients of as well as our tomorrow.

For example, 177Lu-DOTA-TATE is a very exciting drug. Could we potentially use other therapies or other alpha emitters, for example, other types of radiolabeled therapies to improve patient outcomes? Those studies are ongoing. Alpha therapies, for example, have shown promise in prostate cancer. That’s being tested in neuroendocrine cancers. The role for other types of somatostatin receptors with other radiolabeled therapies is something to look out for that we’re all excited about.

We’re constantly looking for other targeted approaches as well. Tons of work, for example, on CAR [chimeric antigen receptor] T cells, which haven’t panned out in terms of finding the right antigen for neuroendocrine cancers, but that’s something to be mindful of. There are other types of VEGF approaches. Surufatinib is very exciting, and maybe combinations with those VEGF inhibitors could be something to look out for. It’s very important to try to use big databases to help us understand what we could learn from big patient populations of sequencing of treatments and when the right time is for these different therapies. That’s where the money is for neuroendocrine cancers: to try to understand what’s the right approach for all these therapies that we have, to better build on that, and to give a better outline of when we should give these therapies and to whom.

The unmet needs for NETs [neuroendocrine] are many. The good news is our patients can live for a very long time. The not-so-good news is that they have to endure a lot of adverse effects sometimes from all these therapies. Patient-reported outcomes and quality-of-life questionnaires are really important.

I always want to give a plug for the caregiver. There’s an unmet need to make sure we understand that these diseases are family diseases. It’s not just the patient population and the biological and clinical needs that patients have but also the emotional and psychological needs that come along with such a diagnosis and a chronic disease and focusing on the whole family. Many of our patients are quite young. With young patients and the financial toxicities that some of our patients endure, we have to study more. Taking care of the patient as a whole is something that I’m passionate about.

Lastly, we’re constantly trying to get to the cure. We want to be proud of the work that’s been done in this disease. No other GI [gastrointestinal] cancer has had so much promise like neuroendocrine cancers. We’ve talked about many of them today with surufatinib, other VEGF inhibitors, and PRRT. They’ve completely changed the natural history of this disease, which is incredibly exciting. But we still have more work to do. Finding more novel therapies and potential approaches with fewer toxicities is something that we’re all mindful of and passionate about.

Transcript Edited for Clarity