We report the impact of 177Lu-DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standarddose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n5114)were asked to recordthe 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 mixedmodel for repeated measures. Results: 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 d per 4 wk, respectively, compared with 0.99, 1.44, and 2.54 d for high-dose octreotide LAR. The mean differences were 3.11 d (95% CI, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 d (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 d (0.08-3.88; P = 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. Conclusion: 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 progressivemidgut neuroendocrine tumors, compared with highdose octreotide LAR, supporting a beneficial effect of 177Lu-DOTATATE on health-related quality of life. COPYRIGHT
|Number of pages||7|
|Journal||Journal of Nuclear Medicine|
|Publication status||Published - 1 Dec 2021|
Bibliographical noteFunding Information:
Research was funded by Advanced Accelerator Applications (AAA), a Novartis company. AAA develops and markets treatments for cancer. Jonathan Strosberg reports personal fees from Lexicon, Ipsen, and Novartis outside the submitted work. Rajaventhan Srira-jaskanthan reports educational grants from AAA outside the submitted work. Ghassan El-Haddad reports personal fees from AAA outside the submitted work. Edward Wolin reports personal fees from Ipsen, AAA, and Progenics outside the submitted work. Beth Chasen reports personal fees from AAA outside the submitted work. Martyn Caplin reports grants and personal fees from AAA and personal fees from Novartis and Ipsen outside the submitted work. Andrew Hendifar reports personal fees from AAA and from Merck, grants from PANCAN, and grants and personal fees from Ipsen outside the submitted work. Philippe Ruszniewski reports personal fees from AAA outside the submitted work. Paola Santoro is employed by AAA. Per Broberg is employed by AAA. Oscar Leeu-wenkamp is employed by AAA, owns shares in AAA, and has received personal fees from Galderma outside the submitted work. Eric Krenning reports receiving travel, accommodations, or expenses from AAA and has held patents, royalties, or other intellectual property from AAA. This work was supported by AAA. Under the direction of the authors, Dr. Martin Guppy, an employee of Oxford PharmaGenesis, provided writing assistance for this article with funding from AAA. AAA reviewed for scientific accuracy. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright: © 2021 by the Society of Nuclear Medicine and Molecular Imaging.