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

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.