Insights From: Heloisa P. Soares, MD, UNM Comprehensive Cancer Center; Jonathan R. Strosberg, MD, Moffitt Cancer Center; Timothy J. Hobday, MD, Mayo Clinic College of Medicine and Science
Timothy J. Hobday, MD: I think we still struggle to control some of our patients who have refractory hormonal syndromes with our current therapies. And so, an unmet need is to further help improve our patients’ quality of life as they live with these cancers.
Another unmet need is really trying to personalize our therapy. We have a number of treatments that can be helpful. But sometimes they are not for each individual patient. Trying to come up with predictors of benefit to various therapies, to more closely match or better predict what patients will respond to which therapy, is another unmet need—rather than treating everybody in a similar fashion.
I think we also need to increase the recognition that these patients need to be cared for at expert centers, with multidisciplinary expertise in caring for these patients, which can also facilitate better enrollment to clinical trials that could advance the science and care for these patients.
Jonathan R. Strosberg, MD: I think there are still a lot of unmet needs. One is simply learning how to best tailor the current treatments that we have—learning how to sequence them and, maybe even more importantly, learning how to predict which patients will respond to which treatment. That’s going to be a real challenge, as we develop more and more treatments for this disease. But beyond that, I think we need treatments that work better and have a better therapeutic index. Some of the treatments that we have still have a lot of toxicities. They have a negative impact on quality of life, and quality of life is particularly important in patients with slow-growing tumors or those with a relatively good life expectancy. We really need to develop treatments that are less toxic and less risky.
The acute need, though, is perhaps greatest for poorly differentiated neuroendocrine carcinomas. We really haven’t moved beyond first-line platinum-etoposide therapy. These are really aggressive tumors, and we need to develop new treatments. It could be that immunotherapy with checkpoint inhibitors works better in that population than in well-differentiated neuroendocrine tumors. I’m happy to say that there’s a large number of new studies that really, for the first time, are targeting the poorly differentiated neuroendocrine carcinoma population.
Heloisa P. Soares, MD: There are a few unmet needs in neuroendocrine tumors. For poorly differentiated high-grade tumors, we don’t have a lot of options. We have our first-line therapy. After that, it’s almost like dealer’s choice. Different oncologists choose different things, using a small-cell lung cancer algorithm. So, we definitely need more trials and more options for poorly differentiated high-grade tumors. In the low-grade neuroendocrine tumors, I think we’ll have to decide where peptide receptor radionuclide therapy will play a role, in terms of timing of treatment. I also believe that we need more options for midgut tumors. For pancreatic tumors, we now have several lines of treatment. But that’s not the same for midgut. We also don’t have an established role for treatment in the neoadjuvant or adjuvant setting for patients who have been completely resected. These are all unmet needs, and there is plenty of work that we can do.
Jonathan R. Strosberg, MD: The next research question is how to sequence treatments for neuroendocrine tumor patients. There’s a number of trials that have started accruing patients. The COMPETE study is looking at lutetium-177 DOTATOC, a slightly different radiolabeled somatostatin analog from lutetium-177 DOTATATE, compared with everolimus in nonfunctioning gastroentero-pancreatic neuroendocrine tumors. Another study is looking at 5-FU/streptozocin versus everolimus in pancreatic neuroendocrine tumors. There are other studies comparing active regimens. That’s a very important development.