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Eur J Nucl Med Mol Imaging. 2020 Mar 2. doi: 10.1007/s00259-020-04709-x. [Epub ahead of print]

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.

Author information

1
Gastrointestinal Department/Neuroendocrine Tumor Division, Moffitt Cancer Center, Tampa, FL, USA. jonathan.strosberg@moffitt.org.
2
Department of Medicine - Med/Oncology, Stanford University Medical Center, Stanford, CA, USA.
3
Department of Internal Medicine/Hematology/Oncology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
4
Department of Gastrointestinal Medicinal Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
5
Department of Radiology, The University of Iowa, Iowa City, IA, USA.
6
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
7
Department of Nuclear Medicine, Zentralklinik Bad Berka, Bad Berka, Germany.
8
Department of Gastroenterology and Tumour Neuroendocrinology, Royal Free Hospital, London, UK.
9
Division of Gastroenterology and Pancreatology, Hôpital Beaujon, Clichy, France.
10
Department of Clinical Nuclear Medicine, Excel Diagnostics Imaging Clinic, Houston, TX, USA.
11
Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA.
12
Department of Hepatology, University Hospitals and KU Leuven, Leuven, Belgium.
13
Hematology Oncology Division, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA.
14
Department of Gastroenterology and General Internal Medicine, King's College Hospital - NHS Foundation Trust, London, UK.
15
Division of Hepatology and Gastroenterology, Charite-Universitätsmedizin Berlin, Berlin, Germany.
16
Department of Nuclear Medicine, Hospital Universitari de Bellvitge, Barcelona, Spain.
17
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
18
Department of Medical Oncology, MD Anderson Cancer Center, Madrid, Spain.
19
Department of Medical Oncology, Beatson Oncology Centre, Glasgow, UK.
20
Department of Nuclear Medicine Therapy and Endocrinology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.
21
Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
22
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
23
GI Division, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
24
Nuclear Medicine Department, Hôtel Dieu, University Hospital, Nantes, France.
25
Medical Imaging, Oncology University Institut Claudius Regaud, Toulouse, France.
26
Division of Imaging and Interventional Radiology, Imperial College London, London, UK.
27
Department of Endocrine Oncology and Nuclear Medicine, Institut Gustave Roussy, Villejuif, France.
28
Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
29
Department of Nuclear Medicine, Hôpital de la Timone, Marseille, France.
30
Department of Nuclear Medicine, Oregon Health & Science University, Portland, OR, USA.
31
Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
32
Department of Internal Medicine, The University of Iowa, Iowa City, IA, USA.
33
Department of Nuclear Medicine, Royal Free Hospital, London, UK.
34
Nuclear Medicine Department, University Hospitals and KU Leuven, Leuven, Belgium.
35
Division of Nuclear Medicine, Istituto Europeo di Oncologia, Milan, Italy.
36
Department of Nuclear Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
37
Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden.
38
Department of Medical Information, Advanced Accelerator Applications, a Novartis Company, Geneva, Switzerland.
39
Advanced Accelerator Applications, a Novartis Company, Geneva, Switzerland.
40
Research and Development, Advanced Accelerator Applications, a Novartis Company, Geneva, Switzerland.
41
Department of Clinical Development, Advanced Accelerator Applications, a Novartis Company, Geneva, Switzerland.
42
Department of Nuclear Medicine, Cyclotron Rotterdam BV, Erasmus University Medical Center, Rotterdam, Netherlands.

Abstract

PURPOSE:

To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate.

METHODS:

In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression.

RESULTS:

Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden.

CONCLUSIONS:

177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11.

KEYWORDS:

177Lu-Dotatate; Liver tumour burden; NETTER-1; Neuroendocrine tumour; Octreotide

PMID:
32123969
DOI:
10.1007/s00259-020-04709-x

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