Peptide receptor radionuclide therapy for refractory midgut neuroendocrine tumors

This article is from the NEJM Journal Watch Review of Peptide Receptor Radionuclide Therapy for Refractory Mid-Gut Neuroendocrine Tumors Peptide Receptor Radionuclide Therapy for Refractory Mid-gut Neuroendocrine Tumors by David H.
Ilson, MD, PhD1 The new study supports previous findings that peptide receptor radionuclide therapy (PRRT) has better progression-free survival than systemic therapy, but not overall survival
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PRRT has been approved for the treatment of well-differentiated midgut neuroendocrine tumors that have progressed after somatostatin analog (SSA) therapy based on the prolongation of progression-free survival (PFS) observed in the NETTER-1 trial (NEJM JW Oncol Hematol Mar 2017 and N Engl J Med 2017;376:125)
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The therapy has since been approved for the treatment of low- or intermediate-grade gastroenteropancreatic neuroendocrine tumors
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However, recent results from the NETTER-1 trial did not demonstrate that PRRT was superior to escalating-dose SSA in overall survival (OS) in patients with refractory midgut neuroendocrine tumors (NEJM JW Oncol Hematol Feb 2022 and Lancet Oncol 2021; 22: 1752)
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This time, Italian researchers published the results of a multicenter retrospective study of 508 patients with gastroenteropancreatic neuroendocrine tumors with disease progression after SSA who received PRRT or systemic therapy in second-line therapy (Applied ).
Targeted drugs [everolimus or sunitinib] or chemotherapy [temozolomide, fluorinated pyrimidines, or platinum-based drugs])
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More patients received PRRT than received targeted drugs or chemotherapy (65% vs.
35%)
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The prevalence of pancreatic-derived neuroendocrine tumors was higher in the targeted drug/chemotherapy group than in PRRT (77% vs.
37%)
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Most patients had WHO grade 1-2 tumors (90%-95%), and most patients had tumors with a Ki-67 proliferation index ≤10% (70%-86%)
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At a median follow-up of 90 months, median PFS was greater in the PRRT group than in the systemic group (2.
5 years vs.
0.
7 years; hazard ratio, 0.
35; P<0.
001), but there was no improvement in median OS (12.
0 in each group, respectively).
years and 11.
6 years)
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Similar results were observed in the propensity score-matched population
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In a multivariate analysis of all patients, regardless of tumor location (pancreas or bowel), tumor status (functional or non-functional), or tumor grade (grade 1 or 2 with Ki-67 index ≤10%), PFS improvement was independently associated with PRRT
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Comments This important study supports the observations of the NETTER-1 trial that in patients with disease progression following SSA, PRRT resulted in a significant improvement in PFS, but not OS, compared with systemic therapy
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The study's observations covered pancreatic and intestinal primary tumors and suggest that PRRT should be used before other systemic therapies
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An ongoing randomized trial is also comparing PRRT with systemic therapy in gastroenteropancreatic neuroendocrine tumors that have progressed after SSA therapy
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Reviewed article Pusceddu S et al.
Association of upfront peptide receptor radionuclide therapy with progression-free survival among patients with enteropancreatic neuroendocrine tumors.
JAMA Netw Open 2022 Feb 24; 5:e220290.
(https://doi.
org/10.
1001/jamanetworkopen .
2022.
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