177Lu-DOTATATE achieves 45% ORR, 80% DCR in advanced foregut and hindgut neuroendocrine tumors.
Background
Advanced neuroendocrine tumors (NETs) of the foregut and hindgut represent a significant global disease burden, particularly within Asian populations. Despite this, these specific patient cohorts are often underrepresented in clinical trials evaluating peptide receptor radionuclide therapy (PRRT) for gastroenteropancreatic (GEP) NETs. Current standard-of-care options can be limited for these advanced stages, highlighting a critical need for effective, well-characterized treatments. PRRT, utilizing radiolabeled somatostatin analogs like 177Lu-DOTATATE, targets somatostatin receptors (primarily SSTR2) overexpressed on NET cells, offering a targeted therapeutic approach.
Study Design
This single-center retrospective study evaluated the efficacy and safety of PRRT in 34 consecutive patients (median age 56 years) with biopsy-proven metastatic foregut (n=16) and hindgut (n=18) NETs. Patients received up to four cycles of 177Lu-DOTATATE (7.4 GBq/cycle) administered intravenously every 6-8 weeks, alongside nephroprotection. Interim and end-of-treatment 68Ga-DOTANOC PET/CT scans were used for response evaluation, based on RECIST v1.1 criteria. Key endpoints included objective response rate (ORR), disease control rate (DCR), best biochemical response, toxicity profile, quality-of-life scores, progression-free survival (PFS), and overall survival (OS).
Results
A total of 111 cycles of 177Lu-DOTATATE were administered across the 34 patients, with a median cumulative activity of 26.5 GBq. After a median follow-up of 45.3 months, the treatment yielded significant clinical benefits. The best objective response rate (ORR) was 45%, and the disease control rate (DCR) reached 80%. Patients experienced a median progression-free survival (PFS) of 29.7 months (95% CI, 20.3-39.1). Survival outcomes were also encouraging, with 1-year overall survival (OS) rates at 93.8% (95% CI, 85.4-100) and 5-year OS rates at 53.6% (95% CI, 28.6-78.6).
Key Findings
- 177Lu-DOTATATE achieved an objective response rate (ORR) of 45% in advanced foregut and hindgut NETs.
- The disease control rate (DCR) for 177Lu-DOTATATE was 80%.
- Median progression-free survival (PFS) was 29.7 months (95% CI, 20.3-39.1).
- 1-year overall survival (OS) rate was 93.8% (95% CI, 85.4-100).
- Only five patients experienced Grade 3 adverse events, indicating a favorable safety profile.
Why It Matters
This real-world data provides crucial evidence supporting the efficacy and safety of 177Lu-DOTATATE PRRT for advanced foregut and hindgut NETs, particularly in Asian populations often underrepresented in larger trials. Clinicians now have stronger justification to consider PRRT as a viable and effective treatment option for these specific NET subtypes, potentially improving patient outcomes in regions where data has been sparse. The observed high DCR and impressive median PFS suggest that this established protocol can offer durable disease control, extending beyond what might be expected from conventional therapies alone. This reinforces the current 7.4 GBq/cycle dosing regimen as effective.
177lu-dotatate
neuroendocrine-tumors
net
prrt
foregut-net
hindgut-net