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

被引：93

作者：

Strosberg, Jonathan ^{[1
]}

Kunz, Pamela L. ^{[2
]}

Hendifar, Andrew ^{[3
]}

Yao, James ^{[4
]}

Bushnell, David ^{[5
]}

Kulke, Matthew H. ^{[6
]}

Baum, Richard P. ^{[7
]}

Caplin, Martyn ^{[8
]}

Ruszniewski, Philippe ^{[9
]}

Delpassand, Ebrahim ^{[10
]}

Hobday, Timothy ^{[11
]}

Verslype, Chris ^{[12
,13
]}

Benson, Al ^{[14
]}

Srirajaskanthan, Rajaventhan ^{[15
]}

Pavel, Marianne ^{[16
]}

Mora, Jaume ^{[17
]}

Berlin, Jordan ^{[18
]}

Grande, Enrique ^{[19
]}

Reed, Nicholas ^{[20
]}

Seregni, Ettore ^{[21
]}

Paganelli, Giovanni ^{[22
]}

Severi, Stefano ^{[22
]}

Morse, Michael ^{[23
]}

Metz, David C. ^{[24
]}

Ansquer, Catherine ^{[25
]}

Courbon, Frederic ^{[26
]}

Al-Nahhas, Adil ^{[27
]}

Baudin, Eric ^{[28
]}

Giammarile, Francesco ^{[29
]}

Taieb, David ^{[30
]}

Mittra, Erik ^{[31
]}

Wolin, Edward ^{[32
]}

O'Dorisio, Thomas M. ^{[33
]}

Lebtahi, Rachida ^{[34
]}

Deroose, Christophe M. ^{[35
,36
]}

Grana, Chiara M. ^{[37
]}

Bodei, Lisa ^{[38
]}

Oberg, Kjell ^{[39
]}

Polack, Berna Degirmenci ^{[40
]}

He, Beilei ^{[41
]}

Mariani, Maurizio F. ^{[42
]}

Gericke, Germo ^{[42
]}

Santoro, Paola ^{[43
]}

Erion, Jack L. ^{[41
]}

Ravasi, Laura ^{[42
]}

Krenning, Eric ^{[44
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Neuroendocrine Tumor Div, Gastrointestinal Dept, Tampa, FL 33612 USA

[2] Stanford Univ, Med Ctr, Dept Med Med Oncol, Stanford, CA 94305 USA

[3] Cedars Sinai Med Ctr, Dept Internal Med Hematol Oncol, Los Angeles, CA 90048 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA

[5] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA

[6] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[7] Zent Klin Bad Berka, Dept Nucl Med, Bad Berka, Germany

[8] Royal Free Hosp, Dept Gastroenterol & Tumour Neuroendocrinol, London, England

[9] Hop Beaujon, Div Gastroenterol & Pancreatol, Clichy, France

[10] Excel Diagnost Imaging Clin, Dept Clin Nucl Med, Houston, TX USA

[11] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA

[12] Univ Hosp, Dept Hepatol, Leuven, Belgium

[13] Katholieke Univ Leuven, Leuven, Belgium

[14] Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL USA

[15] Kings Coll Hosp NHS Fdn Trust, Dept Gastroenterol & Gen Internal Med, London, England

[16] Charite Univ Med Berlin, Div Gastroenterol & Hepatol, Berlin, Germany

[17] Hosp Univ Bellvitge, Dept Nucl Med, Barcelona, Spain

[18] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[19] MD Anderson Canc Ctr, Dept Med Oncol, Madrid, Spain

[20] Beatson Oncol Ctr, Dept Med Oncol, Glasgow, Lanark, Scotland

[21] Ist Nazl Tumori, Fdn Ist Ric & Cura Carattere Sci, Dept Nucl Med Therapy & Endocrinol, Milan, Italy

[22] IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Dept Med Oncol, Meldola, Italy

[23] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[24] Hosp Univ Penn, GI Div, 3400 Spruce St, Philadelphia, PA 19104 USA

[25] Univ Hosp, Hotel Dieu, Dept Nucl Med, Nantes, France

[26] Oncol Univ, Inst Claudius Regaud, Med Imaging, Toulouse, France

[27] Imperial Coll London, Div Imaging & Intervent Radiol, London, England

[28] Inst Gustave Roussy, Dept Endocrine Oncol & Nucl Med, Villejuif, France

[29] IAEA, Dept Nucl Sci & Applicat, Vienna, Austria

[30] Hop La Timone, Dept Nucl Med, Marseille, France

[31] Oregon Hlth & Sci Univ, Dept Nucl Med, Portland, OR 97201 USA

[32] Icahn Sch Med Mt Sinai, Dept Med Hematol & Med Oncol, New York, NY 10029 USA

[33] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA

[34] Royal Free Hosp, Dept Nucl Med, London, England

[35] Univ Hosp, Dept Nucl Med, Leuven, Belgium

[36] Katholieke Univ Leuven, Leuven, Belgium

[37] Ist Europeo Oncol, Div Nucl Med, Milan, Italy

[38] Mem Sloan Kettering Canc Ctr, Dept Nucl Med, 1275 York Ave, New York, NY 10021 USA

[39] Uppsala Univ Hosp, Dept Endocrine Oncol, Uppsala, Sweden

[40] Adv Accelerator Applicat, Dept Med Informat, Geneva, Switzerland

[41] Adv Accelerator Applicat, Geneva, Switzerland

[42] Adv Accelerator Applicat, Res & Dev, Geneva, Switzerland

[43] Adv Accelerator Applicat, Dept Clin Dev, Geneva, Switzerland

[44] Erasmus Univ, Med Ctr, Cyclotron Rotterdam BV, Dept Nucl Med, Rotterdam, Netherlands

来源：

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING | 2020年 / 47卷 / 10期

关键词：

Lu-177-Dotatate; Liver tumour burden; NETTER-1; Neuroendocrine tumour; Octreotide; RECEPTOR RADIONUCLIDE THERAPY; NEUROENDOCRINE NEOPLASMS; METASTASES; SURVIVAL;

D O I：

10.1007/s00259-020-04709-x

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-177-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 Lu-177-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 Lu-177-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 Lu-177-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. : NCT01578239, EudraCT: 2011-005049-11

引用

页码：2372 / 2382

页数：11

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