| 1. |
- Strosberg, J., et al.
(author)
-
Phase 3 Trial of Lu-177-Dotatate for Midgut Neuroendocrine Tumors
- 2017
-
In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 376:2, s. 125-135
-
Journal article (peer-reviewed)abstract
- BACKGROUND Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials. gov number, NCT01578239; EudraCT number 2011-005049-11.)
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Strosberg, Jonathan R., et al.
(author)
-
NETTER-1 phase III : Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate
- 2016
-
In: Journal of Clinical Oncology. - Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Kentucky, Lexington, KY USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vet Adm Med Ctr, Iowa City, IA USA. Royal Free Hosp, Pond St, London NW3 2QG, England. Zent Klin Bad Berka, Bad Berka, Germany. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. Univ Uppsala Hosp, Uppsala, Sweden. Adv Accelerator Applicat, New York, NY USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Beaujon Hosp, Clichy, France. Erasmus MC, Rotterdam, Netherlands.. - 0732-183X .- 1527-7755. ; 34:4
-
Journal article (other academic/artistic)
|
|
| 10. |
- Strosberg, Jonathan R., et al.
(author)
-
Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with 177Lu-DOTATATE
- 2021
-
In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:12, s. 1712-1718
-
Journal article (peer-reviewed)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.
|
|
