Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with ¹⁷⁷Lu-DOTATATE

Abstract

We report the impact of 177 Lu-DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome.Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial ( 177 Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177 Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177 Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 days per 4 weeks, respectively, compared with 0.99, 1.44, and 2.54 days for high-dose octreotide LAR. The mean differences were 3.11 days (95% confidence interval, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; P = 0.0413) for flushing, favoring 177 Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusions: In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177 Lu-DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut NETs, compared with high-dose octreotide LAR, supporting a beneficial effect of 177 Lu DOTATATE on HRQoL.

How I Treat Neuroendocrine Tumors

“…Peptide receptor radionuclide therapy: The evidence of PFS benefit from radiolabeled SSA, Lu-DOTATATE was demonstrated in NETTER-1 trial with an interim analysis, also demonstrating OS benefit. 26 Objective response rate was higher among patients on peptide receptor radionuclide therapy PRRT (18 vs. 3%). The most common side effect was nausea (59%) from the amino acid infusions administered during treatment for renal protection.…”

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies

“…Fifteen of 24 (63%) health-related domain scores were significantly different, and all HR were ≤ 0.86, all in favor of the PRRT arm. Furthermore, patient diaries demonstrated a substantial reduction in tumoral symptoms, such as abdominal pain (mean reduction 3.11 days per period of 28 days; p < 0.001), diarrhea (3.11 days; p = 0.0017) and flushing (1.98 days; p = 0.041) [ 73 ]. These data validate PRRT both as a tumor-controlling and symptom-relieving treatment.…”

“…Abdominal pain in NETs is usually caused by tumor volume or intestinal ischemia, due to mesenteric lymph nodes and fibrosis [ 81 ]. The NETTER-1 trial has proven that PRRT is a symptom-relieving treatment [ 72 , 73 ]. Taking into consideration that all patients included in the NETTER-1 trial had radiological progressive disease at baseline, Zandee et al retrospectively studied the effect of 177 Lu-DOTATATE in low-grade metastatic midgut NETs with refractory carcinoid syndrome despite treatment with SSAs and without evidence of radiological disease progression at baseline [ 82 ].…”

Eficacia de lutecio-177 DOTATATE/TOC en pacientes con tumores neuroendocrinos bien diferenciados en estado avanzado. Ensayo clínico fase II

“…Por otra parte, el estudio de fase 3, NETTER-1, comparó 177Lu-DOTATATE versus altas dosis de octreotide en pacientes con tumores neuroendocrinos de intestino medio grado 1 y 2 metastásicos, o localmente avanzados, en progresión (2) y se encontró una mediana de supervivencia libre de progresión mayor para el grupo tratado con 177Lu-DOTATATE comparado con el control (HR de 0,21 (IC 95 0,13-0,33)). Adicionalmente, la tasa de control de enfermedad con 177Lu-DOTATATE fue de 18 contra 3 del brazo de control al final del seguimiento (2).…”

“…Por otra parte, las náuseas y el vómito son atribuibles a la infusión de aminoácidos que se hace como un mecanismo nefroprotector, y generalmente se presentaron durante los dos primeros ciclos de tratamiento. Solamente en un paciente se registró un evento hematológico de severidad 4 (síndrome mielodisplásico), el cual junto con la leucemia es un evento adverso reportado en series anteriores en un 2 (2).…”