The Evolving Treatment Landscape for Extrapulmonary Neuroendocrine Carcinomas

Announcer:
This is Project Oncology on ReachMD. On this episode, we’ll hear from Dr. Namrata Vijayvergia, who will be discussing treatment options for patients with extrapulmonary neuroendocrine carcinomas. Dr. Vijayvergia is an Associate Professor of Hematology and Oncology and the Section Chief of Gastrointestinal Medical Oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania. Here she is now.

Dr. Vijayvergia:
When we talk about what affects the outcomes prognosis of patients with extrapulmonary neuroendocrine carcinomas, I think the most important points that we look at are what is the morphology? We do know small cell morphology has a more aggressive course than the large-cell neuroendocrine carcinomas or non-small cell origins. We also know that the site of origin is very important, right? We do see that tumors that arise in the upper GI, in the stomach area, and in the bile duct area. Because we think some of these cancers may be arising from underlying normal epithelial lining of these areas and they just degenerate or become more aggressive or more dedifferentiated and turn into neuroendocrine cancers, sometimes we have to use treatments from those areas. So, for example, in the GI neuroendocrine cancers, there is more and more data and more and more push to use FOLFIRINOX as a frontline regimen instead of carboplatin and etoposide. We use carboplatin and cisplatin and etoposide just as an extrapolation from the small cell lung cancer world, but we are knowing that oxaliplatin is a much more effective platinum drug in the GI space, and maybe it’s time to use a combination thereof, and I think it’s something that’s become more common. There’s actually a trial in Europe that’s going on trying to study it, so we are seeing studies being done in this phase. And we have a national trial for extrapulmonary neuroendocrine carcinomas of adding immunotherapy—it’s an NCTN study—or whether we add the atezolizumab to the chemotherapy or not. It’s something that’s standard for lung, but we are not extrapolating. We are actually doing the study for extrapulmonary cancers to see if there is an actual benefit, and I think that’s a great step. 

The recent approval of tarlatamab for small cell lung cancer, which is a DLL3-targeted T cell engager therapy, has created waves in extrapulmonary neuroendocrine cancers too, but early on, right? We just saw the results of another DLL3-targeting T cell engager, obrixtamig, in this disease in the extrapulmonary neuroendocrine space, and we found that it is an effective treatment for DLL3-high extrapulmonary neuroendocrine cancer, so it’s not for everyone. So in lung, it’s approved for everybody, but in GI neuroendocrine, the way forward is for the DLL3-high tumors, it seems like, based on these early results. So again, we’re not extrapolating. We are doing these studies, and I think with DLL-targeted agents, is it T cell engager therapy? Is it trying to do antibody drug conjugates, etc.? We’re all very excited.

There were also results of a SEZ 6-targeting antibody drug conjugate, and there was really exciting data about a PD-L1 4-1BB bispecific antibody that was presented at ASCO too. And all of these are early results, but all of these new drugs that are targeting or harnessing the immune system to kill the cancer are being specially run in extrapulmonary neuroendocrine cancers, and that’s a really, really great step. We also are looking forward to the phase 3 studies we just talked about, which answers the questions of what is the best chemo backbone? Is it still platinum etoposide or carboplatin and etoposide, or can we move to a FOLFIRINOX kind of regimen? And then also whether we can add immunotherapy to the frontline regimen. And these are important questions that will be answered over the next few years.

Announcer:
That was Dr. Namrata Vijayvergia talking about how the treatment landscape for extrapulmonary neuroendocrine carcinoma is evolving. To access this and other episodes in our series, visit Project Oncology on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!