دورية أكاديمية
Inaugural Results of the Individualized Screening Trial of Innovative Glioblastoma Therapy: A Phase II Platform Trial for Newly Diagnosed Glioblastoma Using Bayesian Adaptive Randomization.
| العنوان: | Inaugural Results of the Individualized Screening Trial of Innovative Glioblastoma Therapy: A Phase II Platform Trial for Newly Diagnosed Glioblastoma Using Bayesian Adaptive Randomization. |
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| المؤلفون: | Rahman R; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Trippa L; Dana-Farber Cancer Institute, Boston, MA., Lee EQ; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Arrillaga-Romany I; Massachusetts General Hospital, Boston, MA., Fell G; Dana-Farber Cancer Institute, Boston, MA., Touat M; Brigham and Women's Hospital, Boston, MA.; Sorbonne Universite, Hôpitaux Universitaires La Pitié Salpêtrière, Paris, France., McCluskey C; Dana-Farber Cancer Institute, Boston, MA., Wiley J; Dana-Farber Cancer Institute, Boston, MA., Gaffey S; Dana-Farber Cancer Institute, Boston, MA., Drappatz J; University of Pittsburgh, Pittsburgh, PA., Welch MR; Division of Neuro-Oncology, Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons, NewYork-Presbyterian, New York, NY., Galanis E; Mayo Clinic, Rochester, MN., Ahluwalia MS; Miami Cancer Institute, Miami, FL., Colman H; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT., Nabors LB; University of Alabama at Birmingham, Birmingham, AL., Hepel J; Rhode Island Hospital, Providence, RI., Elinzano H; Rhode Island Hospital, Providence, RI., Schiff D; University of Virginia, Charlottesville, VA., Chukwueke UN; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Beroukhim R; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Nayak L; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., McFaline-Figueroa JR; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Batchelor TT; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Rinne ML; Dana-Farber Cancer Institute, Boston, MA., Kaley TJ; Memorial Sloan Kettering Cancer Center, New York, NY., Lu-Emerson C; Maine Medical Center, Portland, ME., Mellinghoff IK; Memorial Sloan Kettering Cancer Center, New York, NY., Bi WL; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Arnaout O; Brigham and Women's Hospital, Boston, MA., Peruzzi PP; Brigham and Women's Hospital, Boston, MA., Haas-Kogan D; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Tanguturi S; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Cagney D; Mater Private, Dublin, Ireland., Aizer A; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Doherty L; Dana-Farber Cancer Institute, Boston, MA., Lavallee M; Dana-Farber Cancer Institute, Boston, MA., Fisher-Longden B; Dana-Farber Cancer Institute, Boston, MA., Dowling S; Dana-Farber Cancer Institute, Boston, MA., Geduldig J; Dana-Farber Cancer Institute, Boston, MA., Watkinson F; Dana-Farber Cancer Institute, Boston, MA., Pisano W; Dana-Farber Cancer Institute, Boston, MA., Malinowski S; Dana-Farber Cancer Institute, Boston, MA., Ramkissoon S; Dana-Farber Cancer Institute, Boston, MA., Santagata S; Brigham and Women's Hospital, Boston, MA., Meredith DM; Brigham and Women's Hospital, Boston, MA., Chiocca EA; Brigham and Women's Hospital, Boston, MA., Reardon DA; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Alexander BM; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Ligon KL; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA., Wen PY; Dana-Farber Cancer Institute, Boston, MA.; Brigham and Women's Hospital, Boston, MA. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Dec 20; Vol. 41 (36), pp. 5524-5535. Date of Electronic Publication: 2023 Sep 18. |
| نوع المنشور: | Randomized Controlled Trial; Clinical Trial, Phase II; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Glioblastoma*/pathology , Brain Neoplasms*/therapy, Humans ; Random Allocation ; Bayes Theorem ; ErbB Receptors/genetics ; Biomarkers |
| مستخلص: | Purpose: The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) is a phase II platform trial that uses response adaptive randomization and genomic profiling to efficiently identify novel therapies for phase III testing. Three initial experimental arms (abemaciclib [a cyclin-dependent kinase [CDK]4/6 inhibitor], neratinib [an epidermal growth factor receptor [EGFR]/human epidermal growth factor receptor 2 inhibitor], and CC-115 [a deoxyribonucleic acid-dependent protein kinase/mammalian target of rapamycin inhibitor]) were simultaneously evaluated against a common control arm. We report the results for each arm and examine the feasibility and conduct of the adaptive platform design. Patients and Methods: Patients with newly diagnosed O 6 -methylguanine-DNA methyltransferase-unmethylated glioblastoma were eligible if they had tumor genotyping to identify prespecified biomarker subpopulations of dominant glioblastoma signaling pathways (EGFR, phosphatidylinositol 3-kinase, and CDK). Initial random assignment was 1:1:1:1 between control (radiation therapy and temozolomide) and the experimental arms. Subsequent Bayesian adaptive randomization was incorporated on the basis of biomarker-specific progression-free survival (PFS) data. The primary end point was overall survival (OS), and one-sided P values are reported. The trial is registered with ClinicalTrials.gov (identifier: NCT02977780). Results: Two hundred thirty-seven patients were treated (71 control; 73 abemaciclib; 81 neratinib; 12 CC-115) in years 2017-2021. Abemaciclib and neratinib were well tolerated, but CC-115 was associated with ≥ grade 3 treatment-related toxicity in 58% of patients. PFS was significantly longer with abemaciclib (hazard ratio [HR], 0.72; 95% CI, 0.49 to 1.06; one-sided P = .046) and neratinib (HR, 0.72; 95% CI, 0.50 to 1.02; one-sided P = .033) relative to the control arm but there was no PFS benefit with CC-115 (one-sided P = .523). None of the experimental therapies demonstrated a significant OS benefit ( P > .05). Conclusion: The INSIGhT design enabled efficient simultaneous testing of three experimental agents using a shared control arm and adaptive randomization. Two investigational arms had superior PFS compared with the control arm, but none demonstrated an OS benefit. The INSIGhT design may promote improved and more efficient therapeutic discovery in glioblastoma. New arms have been added to the trial. |
| معلومات مُعتمدة: | P30 CA008748 United States CA NCI NIH HHS; R01 NS116144 United States NS NINDS NIH HHS; R35 NS105109 United States NS NINDS NIH HHS |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02977780 |
| المشرفين على المادة: | 60UAB198HK (abemaciclib) EC 2.7.10.1 (ErbB Receptors) 0 (Biomarkers) |
| تواريخ الأحداث: | Date Created: 20230918 Date Completed: 20231218 Latest Revision: 20240228 |
| رمز التحديث: | 20240228 |
| DOI: | 10.1200/JCO.23.00493 |
| PMID: | 37722087 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
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| DOI: | 10.1200/JCO.23.00493 |