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Title: Inefficiencies in phase II to phase III transition impeding successful drug development in glioblastoma.
Austin Authors: Balasubramanian, Adithya ;Gunjur, Ashray ;Hafeez, Umbreen ;Menon, Siddharth;Cher, Lawrence M ;Parakh, Sagun ;Gan, Hui K 
Affiliation: Medical Oncology
La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Wellness and Research Centre
Olivia Newton-John Cancer Research Institute
Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: Jan-2021
Date: 2020-12-22
Publication information: Neuro-Oncology Advances 2021; 3(1): vdaa171
Abstract: Improving outcomes of patients with glioblastoma (GBM) represents a significant challenge in neuro-oncology. We undertook a systematic review of key parameters of phase II and III trials in GBM to identify and quantify the impact of trial design on this phenomenon. Studies between 2005 and 2019 inclusive were identified though MEDLINE search and manual bibliography searches. Phase II studies (P2T) were restricted to those referenced by the corresponding phase III trials (P3T). Clinical and statistical characteristics were extracted. For each P3T, corresponding P2T data was "optimally matched," where same drug was used in similar schedule and similar population; "suboptimally matched" if dis-similar schedule and/or treatment setting; or "lacking." Phase II/III transition data were compared by Pearson Correlation, Fisher's exact or chi-square testing. Of 20 P3Ts identified, 6 (30%) lacked phase II data. Of the remaining 14 P3T, 9 had 1 prior P2T, 4 had 2 P2T, and 1 had 3 P2T, for a total of 20 P3T-P2T pairs (called dyads). The 13 "optimally matched" dyads showed strong concordance for mPFS (r2 = 0.95, P < .01) and mOS (r2 = 0.84, P < .01), while 7 "suboptimally matched" dyads did not (P > .05). Overall, 7 P3Ts underwent an ideal transition from P2T to P3T. "Newly diagnosed" P2Ts with mPFS < 14 months and/or mOS< 22 months had subsequent negative P3Ts. "Recurrent" P2Ts with mPFS < 6 months and mOS< 12 months also had negative P3Ts. Our findings highlight the critical role of optimally designed phase II trials in informing drug development for GBM.
DOI: 10.1093/noajnl/vdaa171
ORCID: 0000-0001-7319-8546
Journal: Neuro-Oncology Advances
PubMed URL: 33543145
Type: Journal Article
Subjects: clinical trials
drug development
phase II
phase III
trial design
Appears in Collections:Journal articles

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