Treatment Updates Move Neuroendocrine Tumor Paradigm Forward

Syma Iqbal, MD

Although the incidence of neuroendocrine tumors (NETs) has increased, clinicians can better manage patients with midgut tumors following the FDA approval of Lutathera (lutetium Lu 177 dotatate), which has now demonstrated an overall survival (OS) benefit, explained Syma Iqbal, MD.

“There has really been a boom over the last few years, where we've gone from somatostatin analogues to peptide receptor-radionucleotide therapy (PRRT), which is a really effective therapy that is approved in the United States,” said Iqbal, an associate professor of clinical medicine at the Keck School of Medicine of University of Southern California.

The January 2018 FDA approval of Lutathera was based on a 79% decrease in the risk of progression or death compared with high-dose octreotide seen in the phase III NETTER-1 trial.¹ Updated data from this study, which were presented at the 2018 ASCO Annual Meeting, indicated 30 PFS events and 78 PFS events in the Lutathera and octreotide arms, respectively (HR, 0.21; 95% CI, 0.14-0.33; P <.0001).² The median OS was not reached with Lutathera, compared with 27.4 months in the control arm.

There was also a longer time to decline in the Lutathera arm based on global health status (HR, 0.406; P = .0006), physical functioning (HR, 0.518; P = .0147), role functioning (HR, 0.580; P = .0298), and fatigue (HR, 0.621; P = .0297).

OncLive: What refinements need to be made in terms of a NET diagnosis?

How has the treatment landscape of NETs changed?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Gastrointestinal Cancers, Iqbal discussed the evolving treatment paradigm of NETs.Iqbal: It takes 5 to 7 years for patients to get a diagnosis from when they first start experiencing symptoms. Oncologists don't diagnose these patients, but given that the incidence is increasing, there needs to be more education, perhaps from folks who are seeing these patients, such as gastroenterologists and primary care physicians. These patients present a very odd constellation of symptoms. They're given all sorts of other diagnoses before they present with their disease. Unfortunately, by then, most of these folks end up presenting with metastatic disease. Education in that diagnostic area is an important part of finding earlier-stage disease.This used to be a very rare disease that oncologists hardly saw, but the incidence has been increasing. We're also identifying it better. This was a disease where we had no options for quite a while. We would basically tell patients that we would watch them if they had a slow-growing disease. That was uncomfortable for patients and for oncologists.

On top of that, we've had clinical trials that have demonstrated the activity of targeted therapies, mTOR inhibitors, and VEGF inhibitors. Suddenly, we have several treatment options. This was a disease that used to be primarily treated by surgeons, and eventually radiologists, as we were doing local regional therapy, ablating, etc.

How would you define the addition of PRRT to the field?

We don’t clearly know how to sequence these options. A patient who has well-differentiated, low-grade disease is going to live a very long time, but they're probably going to go through multiple lines of treatment. That's where we need to figure out how to best sequence these therapeutics, so individuals can get to the next line if they need it in the future. It's a really exciting area.PRRT has been the biggest thing that has happened. The randomized NETTER-1 trial looked at Lutathera versus octreotide and showed essentially a 0.2 HR [for PFS]. I don't think I've ever seen an HR like that before. The therapy has offered a significant benefit to these patients as a very well-tolerated regimen. Given the FDA approval, this will be something that's used fairly often, given how well patients have done with it in terms of long-term benefit.

The field also needs more in terms of identifying which patients are going to respond to what therapy now that we have options. Immunotherapy is also coming into the mix, both in low- and high-grade tumors. There is still a lot to be explored in this disease.

References

1. Strosberg JR, Wolin EM, Chasen B, et al. NETTER-1 phase III: Efficacy and safety results in patients with midgut neuroendocrine tumors treated with 177Lu-DOTATATE. J Clin Oncol. 2016;34(suppl; abstr 4005).
2. Strosberg JR, Wolin EM, Chasen B, et al. First update on overall survival, progression-free survival, and health-related time-to-deterioration quality of life from the NETTER-1 study: 177Lu-Dotatate vs. high dose octreotide in progressive midgut neuroendocrine tumors. J Clin Oncol. 2018;36(suppl; abstr 4099).