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- Pavel, M. E., et al.
(författare)
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Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome : final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study
- 2017
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Ingår i: Annals of Oncology. - : OXFORD UNIV PRESS. - 0923-7534 .- 1569-8041. ; 28:7, s. 1569-1575
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the phase 3 RADIANT-2 study, everolimus plus octreotide long-acting repeatable (LAR) showed improvement of 5.1 months in median progression-free survival versus placebo plus octreotide LAR among patients with advanced neuroendocrine tumors associated with carcinoid syndrome. The progression-free survival P-value was marginally above the pre-specified threshold for statistical significance. Here, we report final overall survival (OS) and key safety update from RADIANT-2.Patients and methods: The RADIANT-2 trial compared everolimus (10 mg/day, orally; n = 216) versus placebo (n = 213), both in conjunction with octreotide LAR (30 mg, intramuscularly, every 28 days). Patients, unblinded at the time of progression or after end of double-blind core phase following primary analysis, were offered open-label everolimus with octreotide LAR (open-label phase). In the open-label phase, patients had similar safety and efficacy assessments as those in the core phase. For OS, hazard ratios (HRs) with 95% CIs using unadjusted Cox model and a Cox model adjusted for prespecified baseline covariates were calculated.Results: A total of 170 patients received open-label everolimus (143 crossed over from the placebo arm; 27 in the everolimus arm continued to receive the same treatment after unblinding). The median OS (95% CI) after 271 events was 29.2 months (23.8-35.9) for the everolimus arm and 35.2 months (30.0-44.7) for the placebo arm (HR, 1.17; 95% CI, 0.92-1.49). HR adjusted for baseline covariates was 1.08 (95% CI, 0.84-1.38). The most frequent drug-related grade 3 or 4 AEs reported during the open-label phase were diarrhea (5.3%), fatigue (4.7%), and stomatitis (4.1%). Deaths related to pulmonary or cardiac failure were observed more frequently in the everolimus arm.Conclusion: No significant difference in OS was observed for the everolimus plus octreotide LAR and placebo plus octreotide LAR arms of the RADIANT-2 study, even after adjusting for imbalances in the baseline covariates. Clinical Trial Number: NCT00412061, www.clinicaltrials.gov
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- Strosberg, Jonathan R., et al.
(författare)
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Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with 177Lu-DOTATATE
- 2021
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:12, s. 1712-1718
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Tidskriftsartikel (refereegranskat)abstract
- 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 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 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 progressive midgut neuroendocrine tumors, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu-DOTATATE on health-related quality of life.
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