Treatment with the Radiolabelled Somatostatin Analog ¹⁷⁷Lu-DOTATATE for Advanced Pancreatic Neuroendocrine Tumors

Abstract

Background: We evaluated the activity and safety profile of ¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced G1-G2 pancreatic neuroendocrine tumors. Patients and Methods: Fifty-two consecutive patients were treated at two different therapeutic dosages of 18.5 or 27.8 GBq in five cycles, according to the patient's kidney function and bone marrow reserve, which are known to be the critical organs in PRRT. Results: Twenty-six patients received a mean full dosage (FD) of 25.5 GBq (range 20.7-27.8) and 26 a mean reduced dosage (RD) of 17.8 GBq (range 11.1-19.9). Both therapeutic dosages resulted in antitumor activity (disease control rate in the entire case series 81%), with 12% complete response, 27% partial response and 46% stable disease in the FD group, whereas we observed 4% complete response, 15% partial response and 58% stable disease in the RD group. Median progression-free survival was not reached in the FD group and was 20 months in the RD group. No major acute or delayed hematological toxicity occurred. Conclusion:¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy showed antitumor activity in advanced pancreatic neuroendocrine tumors even at a reduced total activity of 18.5 GBq. However, progression-free survival was significantly longer (p = 0.05) after a total activity of 27.8 GBq, which can thus be considered the recommended dosage in eligible patients.

Safety and outcomes of 177Lu‐DOTATATE for neuroendocrine tumours: experience in New South Wales, Australia

“…The estimated median PFS of our patient cohort was lower than rates published in recent studies and could potentially be explained by differences in tumour characteristics. In general, a higher proportion of patients in this evaluation had non‐GEP NET primary sites and tumours with a high Ki‐67 proliferation index, which are associated with poorer PFS, than the published literature.…”

“…Results from the phase III NETTER‐1 trial, published in January 2017, showed that PRRT treatment with 177 Lu‐DOTATATE significantly improved progression‐free survival (PFS) and suggested an overall survival (OS) benefit, when compared with treatment with octreotide long‐acting repeatable in patients with well‐differentiated, metastatic midgut NET . Results from case series have mostly focused on gastroenteropancreatic NET (GEP NET) and have also been encouraging …”

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

“…It is also important to note that the NETTER-1 study described below only applied to midgut NET, including the jejunum, ileum, appendix, and right colon, for which there are currently limited approved targeted therapies. Nevertheless, retrospective analyses of outcome in pancreatic NET suggest similarly impressive survival [35,37]. The neoadjuvant use of PRRT in patients with unresectable or borderline resectable primary pancreatic tumours has also been suggested [38,39].…”

Somatostatin Receptor 2–Targeting Compounds

“…However, analysis of survival data showed that survival in patients with a partial response might be similar to that in patients with stable disease after PRRT (36)(37)(38)(39). With these findings in mind, for the evaluation of a response, one could consider disease control rates (complete response, partial response, and stable disease), which ranged from 62% to 95% in trials including only patients with progressive disease at baseline (38)(39)(40)(41)(42). Figure 2 shows the efficacy of PRRT in a patient with rectal NET with metastases to the liver.…”