# Beyond similarities: overall survival and prognostic insights from [¹⁷⁷Lu]Lu-DOTATOC therapy in neuroendocrine tumors

## TL;DR

This study shows that [177Lu]Lu-DOTATOC is an effective treatment for neuroendocrine tumors with minimal radioactive waste and identifies key factors predicting patient survival.

## Contribution

The study provides new insights into the efficacy and prognostic factors of [177Lu]Lu-DOTATOC therapy for neuroendocrine tumors.

## Key findings

- Median overall survival was 55.2 months for patients treated with [177Lu]Lu-DOTATOC.
- Baseline De Ritis Ratio, ALP, CgA, and prior mTOR-inhibitor therapy were significant prognostic factors for overall survival.
- Disease control rate was 72%, with primary tumor location and CgA affecting progression risk.

## Abstract

Therapy with [177Lu]Lu-DOTATATE is well established for neuroendocrine tumors (NET), but its production generates [177mLu], raising concerns about waste disposal due to its longer half-life. In contrast, [177mLu] is not formed during [177Lu]Lu-DOTATOC production. However, data on overall survival (OS) and prognostic factors for [177Lu]Lu-DOTATOC remain limited, and its efficacy compared to [177Lu]Lu-DOTATATE is uncertain. This study aimed to analyze OS and radiological response in NET patients treated with [177Lu]Lu-DOTATOC.

Monocentric, retrospective analysis of 141 patients with NET (grading: 21% G1, 71% G2, 4% G3, 4% grading unknown; primary: 48% small intestine (SI-NET); 27% pancreas (P-NET); 9% colon/rectum; 1% stomach, 7% lung; 9% CUP-NET) receiving PRRT with [177Lu]Lu-DOTATOC. Cox and logistic regression were used to identify prognostic factors for OS or risk of primary progression.

Death from any cause was observed in 85 of 141 patients (60.3%). Median OS was 55.2 months (SI NET G1-G2: 62.7 months; P-NET G1-G2: 41.2 months; NET G3: 26.3 months). Multivariable Cox regression identified baseline De Ritis Ratio (p < 0.001), ALP (p < 0.001), CgA (p < 0.001) and prior therapy with mTOR-inhibitors (p = 0.005) as significant prognostic factors of OS. Overall response rate was 12% and disease control rate was 72%. In multivariable logistic regression, primary tumor location (p = 0.04) and CgA (p = 0.01) were significant prognostic factors for higher risk of primary progression.

The analysis of OS from routine clinical practice shows that PRRT with [177Lu]Lu-DOTATOC is an effective treatment option for NET patients, while generating minimal [177mLu]. The evaluated prognostic factors could help to identify patients who particularly benefit from shorter follow-up intervals.