Lutetium Lu 177 Dotatate Brings Partial Response in Metastatic BP-NETs

BP-NETs account for 20% to 30% of neuroendocrine tumors.

Lutetium Lu 177 dotatate (Lutathera) yielded antitumors activity in patients with metastatic bronchopulmonary neuroendocrine tumors (BP-NETs), according to real-world study data shared at the 2025 World Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer.¹

Among patients treated with lutetium Lu 177 dotatate (n = 23), partial responses, stable disease, and progressive disease occurred in 17%, 30%, and 23% of patients, respectively.

“In clinical practice, the decision of when to utilize peptide receptor radionuclide therapy (PRRT) varies widely, found here most commonly as a third-line systemic agent,” Giuseppe Maiocco, MD, a resident in the Division of Internal Medicine at the Mayo Clinic, and coauthors wrote in a poster presentation.

What Are the Background and Design of this Real-World Study?

Lutetium Lu 177 dotatate is a PRRT, and has emerged as a promising treatment in NETs with selective targeting of somatostatin receptor–expressing cells.

In April 2024, the FDA approved lutetium Lu 177 dotatate for the treatment of patients 12 years of age or older with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors. ² This regulatory decision represented the first FDA approval of a radioactive drug or radiopharmaceutical for this patient population.

Of note, BP-NETs comprise approximately 20% to 30% of neuroendocrine tumors, and the management of metastatic BPNETs requires substantial tailoring.¹ Accordingly, the objective of this real-world study was to evaluate the real-world use of lutetium Lu 177 dotatate in patients with BPNETs.

In the retrospective analysis, patients with metastatic BP-NETs were treated with PRRT at Mayo Clinic sites in Arizona, Florida, and Minnesota between 2014 and 2025. Notably, tumor grade was defined by Ki-67 score and histology was defined per World Health Organization (WHO) 2017 criteria, respectively.

Primary outcomes included response rates, progression-free survival (PFS), and overall survival (OS). Response rates were assessed by 3-month post-treatment interval restaging imaging and clinician document assessment. PFS was defined as PRRT initiation to any disease progression, last follow-up, or death; OS was defined as PRRT initiation to last follow-up or death.

What Were the Baseline Patient Characteristics?

In the patient population, the median age was 66 years (range, 62-75), 39% were female, and 48% had a history of tobacco use. Metastatic sites included liver (78%), bone (61%), pancreas (9%), and contralateral lung (4%). Additionally, patients had grade 1 (26%), grade 2 (39%), or grade 3 (26%) disease per WHO 2017 criteria. Carcinoid histology was either typical (43%) and atypical (57%). Furthermore, the majority of patients were nonfunctional (70%), had a Krenning scale score of 4 (57%), and an ECOG performance status of 0 (57%). The median number of PRRT treatments was 4 (interquartile range, 2-6). Regarding treatment history, more than half of patients received 2 systemic treatments before PRRT (52%). Preceding treatments included somatostatin analog (100%); chemotherapy (65%), with 43% of patients treated with single-line chemotherapy; everolimus (Afinitor; 43%), and a TKI (9%). Notably, 43% of patients did not receive systemic treatments following PRRT.

What Other Efficacy and Safety Data Were Reported?

In all patients, the median PFS was 10.8 months (95% CI, 7.3-15.9). Moreover, in patients with typical and atypical carcinoid histology, the median PFS was 11.1 months (95% CI, 2.7-19.3) and 8.4 months (95% CI, 6.4-14.7). Those with a Krenning score of 4 and a Krenning score of 3 or less had a median PFS of 14.7 months (95% CI, 9.1-25.8) and 7.3 months (95% CI, 2.7-13.3).

The median OS in all patients was 35.6 months (95% CI, 11.9-50.2). Patients with typical and atypical carcinoid histologies had a median OS of 35.5 months (95% CI, 9.2-not reached [NR]) and 19.8 months (95% CI, 8.5-NR). Patients with a Krenning score of 4 or a Krenning score of 3 or less had a median OS of 24.4 months (95% CI, 13.1-NR) and 16.5 months (95% CI, 4.8-NR).

Regarding safety, the most common treatment-related adverse effects [AEs] included fatigue (35%), nausea (26%), abdominal pain (22%), and decreased appetite (13%).

“[Lutetium Lu 177 dotatate] was well tolerated, with no grade 3 or higher [AEs],” Maiocco and coauthors concluded in the poster presentation.

References

1. Maiocco G, Hazim A, Halfdanarson T, et al. Real-world outcomes of patients with bronchopulmonary neuroendocrine tumors treated with Lutetium Lu-177 dotatate. Presented at: International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract P3.13.32.
2. FDA approves lutetium Lu 177 dotatate for pediatric patients 12 years or older with GEP-NETS. FDA. April 23, 2024. Accessed September 9, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-dotatate-pediatric-patients-12-years-and-older-gep-nets