Efficacy of intra-arterial [ 177 Lu]Lu-DOTATATE vs. continuation intravenous [ 177 Lu]Lu-DOTATATE peptide receptor radionuclide therapy in nonresponding locally advanced inoperable or liver-dominant metastatic gastroenteropancreatic neuroendocrine tumors.
Intra-arterial [177 Lu]Lu-DOTATATE may offer better outcomes than intravenous administration in certain nonresponsive GEP-NET cases, but further trials are needed to confirm these findings.
Where it sits
this study against the rest of the octreotide corpusSummary and findings
This study compared intra-arterial [177 Lu]Lu-DOTATATE PRRT to continued intravenous [177 Lu]Lu-DOTATATE in 33 patients with nonresponsive gastroenteropancreatic neuroendocrine tumors. Group A, receiving intra-arterial treatment, showed higher objective response rates and longer progression-free survival. No major toxicity was observed in either group.
Abstract
<h4>Background</h4>Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) demonstrating liver-dominant inoperable metastatic diseases or locally advanced inoperable tumors may at times show reduced efficacy for intravenous peptide receptor radionuclide therapy (PRRT).<h4>Aims and objectives</h4>To determine and compare the outcome of intra-arterial [ 177 Lu]Lu-DOTATATE PRRT in GEP-NET with locally advanced inoperable primary or liver-dominant metastases who had shown no response after at least two cycles of intravenous [ 177 Lu]Lu-DOTATATE, as compared to those patients who continued intravenous [ 177 Lu]Lu-DOTATATE only.<h4>Materials and methods</h4>GEP-NET patients with locally advanced inoperable primary or liver metastatic disease, who exhibited nonresponsive disease (either stable or progressive disease on anatomical imaging evaluation) after at least two cycles of intravenous [ 177 Lu]Lu-DOTATATE PRRT, were administered intra-arterial [ 177 Lu]Lu-DOTATATE PRRT (group A). For comparison, matched controls [age, gender, primary site, tumor grade, proliferation index, disease burden, and [ 18 F]fluorodeoxyglucose (FDG) PET/computed tomography status] who had received only intravenous [ 177 Lu]Lu-DOTATATE PRRT (group B) were selected retrospectively. The data were compared and analyzed for response assessments across three categories (symptomatic, including various quality-of-life scores; biochemical; and imaging), survival outcomes, and toxicity profiles.<h4>Results</h4>A total of 33 GEP-NET patients (group A-11 and group B-22) were included. Symptomatic alleviation was slightly higher in group A compared with group B (75 vs. 66.8%), with higher quality-of-life (QoL) scores in group A. According to RECIST 1.1, group A had a 36.3% objective response rate compared with 13.6% in group B. Group A had a higher disease control rate (90.8%) than group B (77.2%). The median progression-free survival (PFS) was significantly longer in group A (not attained) compared with group B (median PFS of 22 months; P < 0.05). No major toxicity was observed in either group.<h4>Conclusion</h4>Intra-arterial [ 177 Lu]Lu-DOTATATE resulted in a higher response rate, symptomatic relief, improved QoL, and prolonged PFS in patients whose disease remained nonresponsive after intravenous [ 177 Lu]Lu-DOTATATE. Prospective randomized controlled trials can further validate the incorporation of intra-arterial PRRT into the management of GEP-NETs.
Background
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with liver-dominant inoperable metastases or locally advanced tumors often show reduced efficacy to intravenous peptide receptor radionuclide therapy (PRRT). This study addresses the potential benefits of intra-arterial administration of [177 Lu]Lu-DOTATATE in such nonresponsive cases. Understanding whether intra-arterial delivery can improve outcomes is crucial for optimizing treatment strategies in these patients.
Methods
The study involved 33 GEP-NET patients who were nonresponsive to at least two cycles of intravenous [177 Lu]Lu-DOTATATE PRRT. Group A (n=11) received intra-arterial [177 Lu]Lu-DOTATATE, while group B (n=22) continued with intravenous treatment. Patients were matched based on age, gender, primary site, tumor grade, proliferation index, disease burden, and FDG PET/CT status. Outcomes were assessed in terms of symptomatic relief, biochemical and imaging responses, survival, and toxicity.
Results
Group A demonstrated a 36.3% objective response rate compared to 13.6% in group B. The disease control rate was 90.8% in group A versus 77.2% in group B. Symptomatic relief was reported in 75% of group A compared to 66.8% in group B, with higher QoL scores in group A. Median progression-free survival was significantly longer in group A, not being reached, compared to 22 months in group B (P < 0.05). No major toxicity was observed in either group.
Interpretation
The intra-arterial administration of [177 Lu]Lu-DOTATATE appears to enhance response rates and prolong progression-free survival compared to continued intravenous treatment in nonresponsive GEP-NET patients. While the effect sizes are statistically significant, the clinical significance needs further exploration through larger, prospective trials. The study's retrospective nature and small sample size limit the generalizability of the findings.
Key findings
- Symptomatic alleviation was 75% in group A vs 66.8% in group B.
- Objective response rate was 36.3% in group A vs 13.6% in group B.
- Disease control rate was 90.8% in group A vs 77.2% in group B.
- Median PFS was not attained in group A vs 22 months in group B, P < 0.05.
- No major toxicity was observed in either group.
Limitations
- Small sample size (n=33).
- Retrospective design.
- Single-site study.
- Nonrandomized patient allocation.