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      Understanding the increasing incidence of neuroendocrine tumors

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          Abstract

          <p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d7836150e97">Neuroendocrine tumors (NETs) are a diverse group of tumors with origins from different primary sites such as gastro-entero-pancreatic, lung and endocrine tissue. Worldwide, their incidence has increased in recent decades. Advances in imaging and better clinical awareness are traditionally attributed to this trend; however, other factors such as genetic and environmental contributors are appreciated as well. </p>

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          Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States.

          Arvind Dasari, Chan Shen, Daniel S. Halperin … (2017)
          The incidence and prevalence of neuroendocrine tumors (NETs) are thought to be rising, but updated epidemiologic data are lacking.
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            Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors.

            Jonathan Strosberg, Ghassan El-Haddad, Edward Wolin … (2017)
            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 ((177)Lu)-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 (177)Lu-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) ((177)Lu-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 (177)Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the (177)Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the (177)Lu-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 (177)Lu-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 (177)Lu-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 (177)Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).
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              Sunitinib malate for the treatment of pancreatic neuroendocrine tumors.

              Eric Raymond, Laetitia Dahan, Jean-Luc Raoul … (2011)
              The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials. We conducted a multinational, randomized, double-blind, placebo-controlled phase 3 trial of sunitinib in patients with advanced, well-differentiated pancreatic neuroendocrine tumors. All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline. A total of 171 patients were randomly assigned (in a 1:1 ratio) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo. The primary end point was progression-free survival; secondary end points included the objective response rate, overall survival, and safety. The study was discontinued early, after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib. Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group (hazard ratio for progression or death, 0.42; 95% confidence interval [CI], 0.26 to 0.66; P<0.001). A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied. The objective response rate was 9.3% in the sunitinib group versus 0% in the placebo group. At the data cutoff point, 9 deaths were reported in the sunitinib group (10%) versus 21 deaths in the placebo group (25%) (hazard ratio for death, 0.41; 95% CI, 0.19 to 0.89; P=0.02). The most frequent adverse events in the sunitinib group were diarrhea, nausea, vomiting, asthenia, and fatigue. Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00428597.).
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                Author and article information

                Journal
                Title: Expert Review of Endocrinology & Metabolism
                Abbreviated Title: Expert Review of Endocrinology & Metabolism
                Publisher: Informa UK Limited
                ISSN (Print): 1744-6651
                ISSN (Electronic): 1744-8417
                Publication date Created: September 03 2023
                Publication date (Electronic): July 19 2023
                Publication date (Print): September 03 2023
                Volume: 18
                Issue: 5
                Pages: 377-385
                Affiliations
                [1 ]Attending Hematology-Oncology, King’s Daughters Medical Center, Ashland, KY, USA
                [2 ]Division of Hematology- Oncology, Mayo Clinic Jacksonville Campus, Jacksonville, FL, USA
                [3 ]Division of Hematology- Oncology, Mayo Clinic, Mayo Clinic Cancer Center, Rochester, MN, USA
                [4 ]Division of Medical Oncology, Mayo Clinic Arizona, Phoenix, AZ, USA
                Article
                DOI: 10.1080/17446651.2023.2237593
                PubMed ID: 37466336
                SO-VID: e68f29ac-51d1-4937-bc36-42a3ad281887
                Copyright © © 2023
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