Efficacy of 177Lu-Dotatate Induction and Maintenance Therapy of Various Types of Neuroendocrine Tumors: A Phase II Registry Study

Abstract

Peptide receptor radionuclide therapy (PRRT) has been recently established as a treatment option for progressive gastro-entero-pancreatic neuroendocrine tumors (NETs) including four 200 mCi induction cycles. The purpose of this phase 2 trial is to expand use of PRRT to different types of NETs with the application of dose adjustment and evaluate value of maintenance therapy in patients who had disease control on induction therapy. Forty-seven PRRT naïve NET patients with different primary origin received 177Lu-DOTATATE induction therapy, ranging from 75 to 150 mCi per cycle, based on patients’ clinical status such as liver and renal function, extent of metastases, and previous therapies. Thirty-four patients underwent additional maintenance therapy (50–100 mCi per cycle) following induction course until they developed disease progression. The estimated median progression-free survival (PFS) was 36.1 months. The median PFS in our MNET subgroup was 47.7 months, which is markedly longer than NETTER-1 trial with median PFS of 28.4 months. The median PFS was significantly longer in patients who received PRRT as first-line treatment after disease progression on somatostatin analogs compared to patients who received other therapies first (p-value = 0.04). The total disease response rate (DRR) and disease control rate (DCR) was 32% and 85% based on RECIST 1.1 and 45% and 83% based on Choi criteria. This trial demonstrates longer PFS with the addition of low dose maintenance therapy to induction therapy compared to NETTER-1 trial that only included induction therapy. Also, we observed considerable efficacy of PRRT in various types of advanced NETs.

Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS)

“…The exact reasons for this survival benefit in our study are not entirely clear. However, it might relate to the longer course of 177 Lu-Dotatate, which could have increased the tumor radiosensitivity to β-particles by allowing for reoxygenation of the hypoxic tumor cells and redistribution of the tumor cells into more radiosensitive phases of the cell cycle (Bodei et al 2020 ; Sistani et al 2020 ).…”

The evolution of PRRT for the treatment of neuroendocrine tumors; What comes next?

“…It is apparent from dosimetry and safety that many patients are able to receive and benefit from additional cycles of treatment ( 32 , 33 ). Combination therapies are also an area of interest particularly for patients with poorly differentiated tumors and a number of studies are ongoing.…”

Highly Symptomatic Progressing Cardiac Paraganglioma With Intracardiac Extension Treated With 177Lu-DOTATATE: A Case Report

“…A recent phase II registry study from Sistani G and al (23). suggests a potential benefit of increasing the treatment intervals and the number of cycles, each with a lower activity in comparison to phase III NETTER-1 trial (24).…”