Determining Suitable Radioligand Therapy Use in Neuroendocrine Tumors

CancerNetwork^® spoke with Natasha Bahri, MD, MS, and Daneng Li, MD, about their Hot Topics article titled Casting a Wide NET: When Is the Optimal Time for 177Lu-Dotatate Treatment?, which was published in the November 2024 issue of ONCOLOGY^®. Their article focused on findings related to the use of ¹⁷⁷Lutetium-Dotatate (¹⁷⁷Lu-dotatate; Lutathera) in patients with neuroendocrine tumors (NETs) and whether these data supported the use of the novel radioligand therapy for this population.

Bahri is a PGY-5 chief fellow in Medical Oncology and Hematology at City of Hope National Medical Center in Duarte, California. Li is an associate professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center in Duarte, California, and a gastrointestinal editorial board member of ONCOLOGY.

Bahri and Li discussed findings from the phase 3 NETTER-1 trial (NCT01578239) assessing ¹⁷⁷Lu-dotatate for those with inoperable, locally advanced or metastatic, grade 1/2 midgut NETs following progression on long-acting repeatable octreotide therapy.¹ Although these findings established a significant efficacy signal with the radioligand therapy, Li noted that questions remained regarding the sequencing of ¹⁷⁷Lu-dotatate alongside other therapies in the treatment landscape.

The conversation also covered efficacy, safety, and quality-of-life (QOL) data from the phase 3 NETTER-2 trial (NCT03972488), in which investigators assessed high-dose octreotide with or without ¹⁷⁷Lu-dotatate among patients with locally advanced or metastatic, well-differentiated, somatostatin receptor–positive gastroenteropancreatic NETs.² Although data showed improvements in efficacy with the ¹⁷⁷Lu-dotatate combination, there did not appear to be significant differences regarding QOL outcomes between arms.

“We’re waiting for further long-term follow-up information as there was no difference in the QOL metrics. It’s important to think about how these patients’ goals align with the therapy that we’re giving, and if we’re not seeing a difference in the quality of life quite yet, [we need to] look at individual patients, see what their goals are, and match them up to the therapy that we’re giving them,” Bahri stated.

Although the NETTER-1 and NETTER-2 trials demonstrate “great” results associated with efficacy end points such as progression-free survival, the authors noted that it is crucial to weigh these benefits with the potential toxicities when determining suitable candidates for treatment with ¹⁷⁷Lu-dotatate.

“There’s a lot of nuances in terms of who is the ideal patient that’s going to maximally benefit [while] minimizing any risk of serious toxicity in those patients. As a result of that, we’re helping to improve their outcomes to the highest bars possible, whether it’s quality of life or survival,” Li concluded.

References

1. Strosberg J, El-Haddad G, Wolin E, et al; NETTER-1 Trial Investigators. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427
2. Singh S, Halperin D, Myrehaug S, et al; NETTER-2 Trial Investigators. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high-dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2-3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. Lancet. 2024;403(10446):2807-2817. doi:10.1016/S0140-6736(24)00701-3