TY - JOUR
T1 - Comparison of Design, Eligibility, and Outcomes of Neuroendocrine Neoplasm Trials Initiated from 2000 to 2009 vs 2010 to 2020
AU - Das, Satya
AU - Du, Liping
AU - Lee, Cody L.
AU - Arhin, Nina D.
AU - Chan, Jennifer A.
AU - Kohn, Elise C.
AU - Halperin, Daniel M.
AU - Berlin, Jordan
AU - Laferriere, Heather
AU - Singh, Simron
AU - Kunz, Pamela L.
AU - Dasari, Arvind
N1 - Funding Information:
Administrative, technical, or material support: Arhin, Berlin, Singh, Dasari. Supervision: Chan, Halperin, Berlin, Singh, Dasari. Conflict of Interest Disclosures: Dr Das reported receiving personal fees from Novartis, Ipsen, TerSera, and Cancer Expert Now outside the submitted work. Dr Chan reported receiving personal fees from Advanced Accelerator Applications, Ipsen, Lexicon, Crinetics, and Novartis and owning stock in Merck outside the submitted work. Dr Halperin reported receiving grants from Genentech, Tarveda, Novartis, and ITM and personal fees from Novartis, ITM, Chiasma, Curium, Progenics/Lantheus, Chimeric Therapeutics, and Ipsen outside the submitted work. Dr Berlin reported receiving personal fees from IPsen, LSK, Bayer, SeaGen, QED, Clovis, Mirati, Novocure, and AstraZeneca and grants from Immunomedics, Karyopharm, Symphogen, Pfizer, AbbVie, Merck, Array, Pharmacyclics, Lilly, Loxo, Bayer, I-Mab, Atreca, and Dragonfly outside the submitted work. Dr Singh reported receiving grants from Ipsen and Novartis Advanced Accelerator Applications and personal fees from Ipsen outside the submitted work. Dr Kunz reported receiving grants from Brahms (Thermo-Fisher Scientific), Ipsen, Lexicon Pharmaceuticals, Xencor, and Novartis Advanced Accelerator Applications and personal fees from Lexicon Pharmaceuticals, from Acrotech, Ipsen, Novartis Advanced Accelerator Applications, Sun Pharma, Amgen, Genentech, and Crinetics during the conduct of the study and owning stock in Guardant Health outside the submitted work. Dr Dasari reported receiving grants from Novartis, Merck, Eisai, and Hutchison Pharma and personal fees from Novartis, Hutchison Pharma, and Eisai outside the submitted work. No other disclosures were reported. Funding/Support: This work was supported by a Neuroendocrine Tumor Research Foundation Investigator Award (Dr Das) and a Vanderbilt-Ingram Cancer Center GI SPORE Career Enhancement Grant (No. P50 CA236733) (Dr Das). Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/10/27
Y1 - 2021/10/27
N2 - Importance: Neuroendocrine neoplasms (NENs) have historically been grouped homogenously in clinical trials, despite their heterogeneity. Given the adoption of a more advanced pathologic classification system and drug licensure of several targeted therapies over the last decade, information is needed on whether study characteristics of NEN studies have evolved. Objective: To assess changes in study design, eligibility, accrual, sponsorship, and outcomes between phase II or III NEN clinical trials that began enrollment from 2000 to 2009 vs 2010 to 2020. Design, Setting, and Participants: This quality improvement study used a systematic survey of completed studies published between January 1, 2000, and December 31, 2020. Therapeutic phase II and III NEN studies were identified through a database search of Medline (via PubMed), EMBASE (OvidSP), Cumulative Index of Nursing and Allied Health Literature (EBSCOhost), Web of Science (Clarivate), Cochrane Database of Systematic Reviews (Wiley), ClinicalTrials.gov (National Institutes of Health), EU Clinical Trials Register, and National Cancer Institute Clinical Trials. Data were analyzed between March and June 2021. Main Outcomes and Measures: Study characteristic proportions between the 2 enrollment periods. Results: Of 3243 identified studies, 119 studies met criteria for inclusion, of which 117 studies (54 studies that began enrollment between 2000-2009 and 63 studies that began enrollment between 2010-2020) included exact dates of enrollment and were compared. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were less likely to include all NENs (13 studies [21%] vs 34 studies [63%]; P <.001) and more likely to include select NENs (eg, gastrointestinal neuroendocrine tumors, 25 studies [40%] vs 11 studies [20%]; P =.02; pancreatic neuroendocrine tumors, 32 studies [51%] vs 16 studies [30%]; P =.02). Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to specify tumor differentiation (59 studies [98%] vs 34 studies [63%]; P <.001) or Ki-67 index (23 studies [38%] vs 5 studies [9%]; P <.001) in inclusion criteria. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to use progression-free survival (22 studies [35%] vs 9 studies [18%]; P =.04) rather than objective response rate (19 studies [30%] vs 27 studies [53%]; P =.01) as a primary or coprimary end point. Conclusions and Relevance: These findings suggest that NEN trials enrolling over the last decade were more focused on select tumor populations, compared with studies that began enrollment before 2010. Despite this shift, more than 20% of studies still included all NENs. Studying novel agents in specific disease populations may enhance drug development in the field.
AB - Importance: Neuroendocrine neoplasms (NENs) have historically been grouped homogenously in clinical trials, despite their heterogeneity. Given the adoption of a more advanced pathologic classification system and drug licensure of several targeted therapies over the last decade, information is needed on whether study characteristics of NEN studies have evolved. Objective: To assess changes in study design, eligibility, accrual, sponsorship, and outcomes between phase II or III NEN clinical trials that began enrollment from 2000 to 2009 vs 2010 to 2020. Design, Setting, and Participants: This quality improvement study used a systematic survey of completed studies published between January 1, 2000, and December 31, 2020. Therapeutic phase II and III NEN studies were identified through a database search of Medline (via PubMed), EMBASE (OvidSP), Cumulative Index of Nursing and Allied Health Literature (EBSCOhost), Web of Science (Clarivate), Cochrane Database of Systematic Reviews (Wiley), ClinicalTrials.gov (National Institutes of Health), EU Clinical Trials Register, and National Cancer Institute Clinical Trials. Data were analyzed between March and June 2021. Main Outcomes and Measures: Study characteristic proportions between the 2 enrollment periods. Results: Of 3243 identified studies, 119 studies met criteria for inclusion, of which 117 studies (54 studies that began enrollment between 2000-2009 and 63 studies that began enrollment between 2010-2020) included exact dates of enrollment and were compared. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were less likely to include all NENs (13 studies [21%] vs 34 studies [63%]; P <.001) and more likely to include select NENs (eg, gastrointestinal neuroendocrine tumors, 25 studies [40%] vs 11 studies [20%]; P =.02; pancreatic neuroendocrine tumors, 32 studies [51%] vs 16 studies [30%]; P =.02). Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to specify tumor differentiation (59 studies [98%] vs 34 studies [63%]; P <.001) or Ki-67 index (23 studies [38%] vs 5 studies [9%]; P <.001) in inclusion criteria. Studies that began enrollment after 2010, compared with studies that began enrollment from 2000 to 2009, were more likely to use progression-free survival (22 studies [35%] vs 9 studies [18%]; P =.04) rather than objective response rate (19 studies [30%] vs 27 studies [53%]; P =.01) as a primary or coprimary end point. Conclusions and Relevance: These findings suggest that NEN trials enrolling over the last decade were more focused on select tumor populations, compared with studies that began enrollment before 2010. Despite this shift, more than 20% of studies still included all NENs. Studying novel agents in specific disease populations may enhance drug development in the field.
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U2 - 10.1001/jamanetworkopen.2021.31744
DO - 10.1001/jamanetworkopen.2021.31744
M3 - Review article
C2 - 34705010
AN - SCOPUS:85118746484
SN - 2574-3805
VL - 4
JO - JAMA Network Open
JF - JAMA Network Open
IS - 10
M1 - 31744
ER -