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Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.


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 (177Lu)-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 177Lu-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) (177Lu-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 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-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 177Lu-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 177Lu-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 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).

SUBMITTER: Strosberg J 

PROVIDER: S-EPMC5895095 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Phase 3 Trial of <sup>177</sup>Lu-Dotatate for Midgut Neuroendocrine Tumors.

Strosberg Jonathan J   El-Haddad Ghassan G   Wolin Edward E   Hendifar Andrew A   Yao James J   Chasen Beth B   Mittra Erik E   Kunz Pamela L PL   Kulke Matthew H MH   Jacene Heather H   Bushnell David D   O'Dorisio Thomas M TM   Baum Richard P RP   Kulkarni Harshad R HR   Caplin Martyn M   Lebtahi Rachida R   Hobday Timothy T   Delpassand Ebrahim E   Van Cutsem Eric E   Benson Al A   Srirajaskanthan Rajaventhan R   Pavel Marianne M   Mora Jaime J   Berlin Jordan J   Grande Enrique E   Reed Nicholas N   Seregni Ettore E   Öberg Kjell K   Lopera Sierra Maribel M   Santoro Paola P   Thevenet Thomas T   Erion Jack L JL   Ruszniewski Philippe P   Kwekkeboom Dik D   Krenning Eric E  

The New England journal of medicine 20170101 2


<h4>Background</h4>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 (<sup>177</sup>Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors.<h4>Methods</h4>We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuro  ...[more]

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