Among patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs) treated with peptide receptor radionuclide therapy (PRRT), laboratory-measured toxic effects are common but not often associated with serious outcomes, according to study results published in JAMA Network Open. In addition, outcomes of PRRT may be favorable when administered to a diverse group of patients with NETs.

In the US, PRRT is approved for the treatment of NETs. However, data on treatment outcomes in this patient population are limited. To address the knowledge gaps, a team of investigators conducted an analysis in which they determined the clinical outcomes of PRRT for patients with NETs within the first 2 years of treatment implementation at a US-based referral center.

Medical records from 2018 to 2020 were collected and laboratory toxic effects were analyzed using the Common Terminology Criteria for Adverse Events version 5.0. Primary outcomes included data before and after PRRT to determine toxic effects in hematologic, liver, and kidney tissues, as well as outcomes in tumor progression, patient progression-free survival, and overall survival.


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A total of 78 patients (median age, 59.8 years; 50.0% men) who received at least 1 dose of PRRT were included in the analysis. The most frequently reported NETs were small bowl tumors (43.6%) and pancreatic tumors (28.2%). Other malignancies included those of the colon, stomach, lungs, and ovaries.

Before initiating PRRT, 49 patients underwent nonsomatostatin analogue systemic chemotherapy, 49 patients underwent liver-director therapy, and 56 patients had the primary tumor resected.

Of the study cohort, 47 patients had at least 1 new toxic effect of grade 2 or greater during the treatment. The most common effects included leukopenia (n=26), anemia (n=16), acute kidney injury (n=12), liver injury (n=12), and thrombocytopenia (n=9).  

Progression on imaging was evident in 25 patients; 5 patients who did not have progression on imaging died during the course of treatment. The median progression-free survival time was 21.6 months for the entire group. Compared with a pancreatic NET, having a small bowel NET was linked to a lower rate of progression-free survival (hazard ratio [HR], 0.19; P =.01).

In addition, patients with small bowel NETs did not reach the median progression-free survival by 22 months, whereas patients with pancreatic or other NETs reached the median progression-free survival by 13.3 months and 21.0 months, respectively (P =.003). Variables including age, sex, tumor grade, prior systemic therapy, prior liver-directed therapy, and prior resection of primary tumor were not significantly associated with progression.

Due to this study’s short follow-up period, the median overall survival was not reached. Ten patients died after completing at least 1 dose of PRRT, 2 patients died after completing 1 cycle, 4 patients died after completing 2 cycles, and 2 patients each died after completing 3 and 4 cycles. Age at NET diagnosis was considered significantly associated with survival following univariable analysis (HR, 1.08; P =.02).

Some study limitations included the small sample size, heterogeneity of the cohort, limited length of the follow-up period, and lack of 4 doses completed by a larger proportion of the cohort.

“Larger and longer prospective studies are needed to further support these findings and determine how to optimally incorporate PRRT into the treatment of metastatic NETs,” the investigators concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Kipnis ST, Hung M, Kumar S, et al. Laboratory, clinical, and survival outcomes associated with peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. JAMA Netw Open. Published online March 23, 2021. doi: 10.1001/jamanetworkopen.2021.2274