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Peptide Receptor Radionuclide Therapy for Refractory Mid-Gut Neuroendocrine Tumors
Peptide receptor radionuclide therapy (PRRT) is approved to treat well-differentiated, midgut neuroendocrine tumors after progression on somatostatin analogue (SSA) therapy, based on improved progression-free survival (PFS) observed in the NETTER-1 trial (NEJM JW Oncol Hematol Mar 2017 and N Engl J Med 2017; 376:125). Approval for the therapy was then extended to treat low- or intermediate-grade gastroenteropancreatic neuroendocrine tumors. However, an update of the NETTER-1 trial did not indicate superior overall survival (OS) with PRRT versus escalated-dose SSA in patients with refractory midgut neuroendocrine tumors (NEJM JW Oncol Hematol Feb 2022 and Lancet Oncol 2021; 22:1752).
Now, Italian investigators report results of a multicenter, retrospective study of 508 patients with gastroenteropancreatic neuroendocrine tumors and disease progression after SSA who received second-line therapy with either PRRT or systemic therapy with a targeted agent (everolimus or sunitinib) or chemotherapy (temozolomide, fluorinated pyrimidines, or platinum agents). More patients received PRRT than targeted agents or chemotherapy (65% vs. 35%). The targeted agents/chemotherapy group more commonly had neuroendocrine tumors of pancreatic origin than did the PRRT group (77% vs. 37%). Most patients had WHO grade 1–2 tumors (90%–95%), and most had tumors with a Ki-67 proliferation index ≤10% (70%–86%).
At a median follow-up of 90 months, median PFS was longer with PRRT than with systemic therapy (2.5 vs. 0.7 years; hazard ratio, 0.35; P<0.001), but median OS was not improved (12.0 and 11.6 years, respectively). Similar results were seen in a propensity-score–matched population. In a multivariate analysis of all patients, improved PFS was independently associated with PRRT use regardless of the tumor site (pancreatic or intestinal), tumor status (functional or nonfunctional), or tumor grade (1 or 2 with Ki-67 index ≤10%).
This important study supports the observation from the NETTER-1 trial of a significant improvement in PFS, but not OS, with PRRT versus systemic therapy after disease progression on SSA. The observation from this study now encompasses both pancreatic and intestinal primaries and addresses the use of PRRT prior to other systemic therapies. Ongoing randomized trials are also comparing PRRT with systemic therapy in gastroenteropancreatic neuroendocrine tumors progressing on SSA.
Pusceddu S et al.
Title: Association of upfront peptide receptor radionuclide therapy with progression-free survival among patients with enteropancreatic neuroendocrine tumors.
Source: JAMA Netw Open 2022 Feb 24; [e-pub]. (Abstract/FREE Full Text)