Laboratory, Clinical, and Survival Outcomes Associated With Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors

Abstract

IMPORTANCE Peptide receptor radionuclide therapy (PRRT) is approved in the US for treatment of gastroenteropancreatic neuroendocrine tumors (NETs), but data on PRRT outcomes within US populations remain scarce. OBJECTIVE To analyze the first 2 years of PRRT implementation at a US-based NET referral center. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted using medical records of patients with metastatic NET receiving PRRT from 2018 through 2020 in a NET program at a tertiary referral center. Included patients were those at the center with metastatic NETs who received at least 1 dose of PRRT over the study period. Laboratory toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. Tumor response was determined using Response Evaluation Criteria in Solid Tumors 1.1. Survival analysis was conducted to identify factors associated with progression-free survival (PFS) and overall survival. Data were analyzed from August 2018 through August 2020. EXPOSURES Receiving 4 cycles of lutetium-177-dotatate infusion, separated by 8-week intervals targeted to 7.4 GBq (200 mCi) per dose. MAIN OUTCOMES AND MEASURES Data were compared from before and after PRRT to determine hematologic, liver, and kidney toxic effects and to assess tumor progression and patient survival. RESULTS Among 78 patients receiving at least 1 dose of PRRT, median (interquartile range) age at PRRT initiation was 59.8 (53.5-69.2) years and 39 (50.0%) were men. The most common primary NET sites included small bowel, occurring in 34 patients (43.6%), and pancreas, occurring in 22 patients (28.2%). World Health Organization grade 1 or 2 tumors occurred in 62 patients (79.5%). Among all patients, 56 patients underwent pretreatment with tumor resection (71.8%), 49 patients received nonsomatostatin analogue systemic therapy (62.8%), and 49 patients received liverdirected therapy (62.8%). At least 1 grade 2 or greater toxic effect was found in 47 patients (60.3%). Median PFS was 21.6 months for the study group, was not reached by 22 months for patients with small bowel primary tumors, and was 13.3 months for patients with pancreatic primary tumors. Having a small bowel primary tumor was associated with a lower rate of progression compared with having a pancreatic primary tumor (hazard ratio, 0.19; 95% CI, 0.07-0.55; P = .01). Median overall survival was not reached. CONCLUSIONS AND RELEVANCE This cohort study of patients with metastatic NETs found that PRRT was associated with laboratory-measured toxic effects during treatment for most patients and (continued) Key Points Question What are the clinical outcomes for patients who receive peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs) in US-based populations? Findings In this cohort study of 78 patients who underwent PRRT, the treatment was associated with transient laboratory-measured toxic effects in most patients. Median progression-free survival was significantly increased for patients with small bowel primary tumors compared with p...

Dose-Limiting Bone Marrow Toxicities After Peptide Receptor Radionuclide Therapy Are More Prevalent in Women Than in Men

“…1,2 However, DLTs occur in a limited number of patients with a particular predilection for bone marrow and kidney toxicity. [1][2][3][4][5][6][7][8][9][10][11][12] In this study, we have demonstrated that after treatment with 177 Lu-DOTATATE, female NET patients have a higher risk of developing DLTs of platelets and hemoglobin than male subjects. The DLTs of thrombocytopenia are defined as platelet counts less than 75 Â 10 9 /L (CTCAE grade ≥2).…”

New Insights in PRRT: Lessons From 2021

“…A case series on 5 patients with bone marrow infiltration of NETs and myelosuppression demonstrated that PRRT could be safe also in these patients when prophylactic peripheral blood stem cell collection was performed before PRRT ( 29 ). In another study, grade 1–2 hematological toxicities were observed in 60.3% of patients and grade 3–4 toxicities were observed in 25 patients (32.1%), without the development of myelodysplasia or the need for dialysis or liver failure ( 27 ).…”

Management of Gastrointestinal Carcinoid Tumors: An Overview

“…Despite optimal treatment with SSAs, patients may still experience diarrhea and flushing, particularly in severe cases [18]. Thus, peptide receptor radionuclide therapy (PRRT) has been considered a second-line treatment option for carcinoid syndrome refractory to SSAs [18][19][20]. Furthermore, PRRT with 177Lu-DOTATATE was approved in 2018 by the FDA for treating gastroenteropancreatic NETs (GEP-NETs), administered intravenously.…”

“…They target somatostatin receptors, which are highly expressed in well-differentiated NETs. Therefore, PRRT is indicated for patients with advanced inoperable well-differentiated GEP-NETs [18][19][20]. Although PRRT is well-tolerated, the most common adverse reactions reported are nausea and vomiting.…”