NEXT STEPS in Peptide Receptor Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumours

Neuroendocrine tumors are relatively slow growing and their histologic grade and differentiation are closely correlated with their clinical behavior. 

Most of these tumors will have progression on somatostatin analogs and subsequent lines of therapy can include everolimus, peptide receptor radionuclide therapy with the addition of lutetium Lu-177 dotatate for all gastroenteropancreatic endocrine tumors, and chemotherapy or sunitinib for pancreatic neuroendocrine tumors will be needed. Optimal sequencing of agents is still up for debate.

The PFS is longer and the quality of life is better for the patients those can stay in the therapy. Since Lu -177 has a tolerable side affect profile, the patients can benefit the long -term therapy.

The phase III trial of peptide receptor radionuclide therapy using Lu-177 dotatate was associated with a greater median progression-free survival with Lu-177 dotatate compared with high-dose octreotide (hazard ratio [HR] = 0.21, P < .001) and a higher objective response rate.

Lu-177 dotatate also provided a significant quality-of-life benefit and improved symptom burden. There was no evidence of renal toxicity, and a small percentage of patients given Lu-177 dotatate developed myelodysplastic syndrome after long-term follow-up (1.8%). This therapy was approved by the U.S. Food and Drug Administration for patients with somatostatin receptor–positive gastroenteropancreatic endocrine tumors in 2018. With this study population, the PFS had been also analysed.

The overall benefit of peptide receptor radionuclide therapy has been supported by other nonrandomized studies.

Next Steps

There is interest in predictive biomarkers for peptide receptor radionuclide therapy to help individualize therapy and provide early evidence of response. Blood-based tests such as the peptide receptor radionuclide therapy prediction quotient and clinical scores hold promise as early markers of response. The recent 2021 NET-CTPM’s executive summary focused on treatment of neuroendocrine tumors in the era of peptide receptor radionuclide therapy, making combination and retreatment strategies the highest priority.

Peptide receptor radionuclide therapy has taken center stage in the management of neuroendocrine neoplasms, and long-term survival data will further strengthen our practice patterns—such as the statistically significant improvement in progression-free survival and clinically meaningful improvement in overall survival observed in NETTER-1.