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.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Oral Abstract Session: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #A4
J Clin Oncol 34, 2016 (suppl 4S; abstr 194)
Jonathan R. Strosberg, Edward M. Wolin, Beth Chasen, Matthew H. Kulke, David L Bushnell, Martyn E. Caplin, Richard P. Baum, Pamela L. Kunz, Timothy J. Hobday, Andrew Eugene Hendifar, Kjell E. Oberg, Maribel Lopera Sierra, Dik J. Kwekkeboom, Philippe B. Ruszniewski, Eric Krenning; Moffitt Cancer Center, Tampa, FL; University of Kentucky, Lexington, KY; The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute, Boston, MA; Veterans Administration Medical Center, Iowa City, IA; Royal Free Hospital, London, United Kingdom; Zentralklinik Bad Berka, Bad Berka, Germany; Stanford University School of Medicine, Stanford, CA; Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Uppsala University Hospital, Uppsala, Sweden; Advanced Accelerator Applications, New York, NY; Erasmus University Medical Center, Rotterdam, Netherlands; Beaujon Hospital, Clichy, France; Erasmus Medical Center, Rotterdam, Netherlands

Abstract Disclosures


Background: Currently, there are limited therapeutic options for patients with advanced midgut neuroendocrine tumors progressing on first-line somatostatin analog therapy. Methods: NETTER-1 is the first Phase III multicentric, randomized, controlled trial evaluating 177Lu-DOTA0-Tyr3-Octreotate (Lutathera) in patients with inoperable, progressive, somatostatin receptor positive midgut NETs. 230 patients with Grade 1-2 metastatic midgut NETs were randomized to receive Lutathera 7.4 GBq every 8 weeks (x4 administrations) versus Octreotide LAR 60 mg every 4-weeks. The primary endpoint was PFS per RECIST 1.1 criteria, with objective tumor assessment performed by an independent reading center every 12 weeks. Secondary objectives included objective response rate, overall survival, toxicity, and health-related quality of life. Results: Enrolment was completed in February 2015, with a target of 230 patients randomized (1:1) in 36 European and 15 sites in the United States. At the time of statistical analysis, the number of centrally confirmed disease progressions or deaths was 23 in the Lutathera group and 67 in the Octreotide LAR 60 mg group. The median PFS was not reached for Lutathera and was 8.4 months with 60 mg Octreotide LAR [95% CI: 5.8-11.0 months], p < 0.0001, with a hazard ratio of 0.21 [95% CI: 0.13-0.34]. Within the current evaluable patient dataset for tumor responses (n = 201), the number of CR+PR was 19 (18.8%) in the Lutathera group and 3 (3.0%) in the Octreotide LAR 60 mg group (p < 0.0004). Although the OS data were not mature enough for a definitive analysis, the number of deaths was 13 in the Lutathera group and 22 in the Octreotide LAR 60 mg group (p < 0.019 at interim analysis) which suggests an improvement in overall survival. Conclusions: The Phase III NETTER-1 trial provides evidence for a clinically meaningful and statistically significant increase in PFS and ORR, and also suggests a survival benefit in patients with advanced midgut NETs treated with Lutathera. Clinical trial information: NCT01578239