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

Abstract

We report the impact of ¹⁷⁷Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. <b>Methods:</b> All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (¹⁷⁷Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], <i>n</i> = 117; high-dose octreotide LAR, <i>n</i> = 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. <b>Results:</b> Patients (intent-to-treat) who received ¹⁷⁷Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For ¹⁷⁷Lu-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; <i>P</i> = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; <i>P</i> = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; <i>P</i> = 0.0413) for flushing, favoring ¹⁷⁷Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. <b>Conclusion:</b> In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with ¹⁷⁷Lu 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 ¹⁷⁷Lu DOTATATE on HRQoL.