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Systematic review of combinations of targeted or immunotherapy in advanced solid tumors

Tan, AC, Bagley, SJ, Wen, PY, Lim, M, Platten, M, Colman, H, Ashley, DM, Wick, W, Chang, SM, Galanis, E, Mansouri, A, Khagi, S, Mehta, MP, Heimberger, AB, Puduvalli, VK, Reardon, DA, Sahebjam, S, Simes, J, Antonia, SJ, Berry, D and Khasraw, Mustafa 2021, Systematic review of combinations of targeted or immunotherapy in advanced solid tumors, Journal for ImmunoTherapy of Cancer, vol. 9, no. 7, pp. 1-14, doi: 10.1136/jitc-2021-002459.

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Title Systematic review of combinations of targeted or immunotherapy in advanced solid tumors
Author(s) Tan, AC
Bagley, SJ
Wen, PY
Lim, M
Platten, M
Colman, H
Ashley, DM
Wick, W
Chang, SM
Galanis, E
Mansouri, A
Khagi, S
Mehta, MP
Heimberger, AB
Puduvalli, VK
Reardon, DA
Sahebjam, S
Simes, J
Antonia, SJ
Berry, D
Khasraw, MustafaORCID iD for Khasraw, Mustafa orcid.org/0000-0003-3249-9849
Journal name Journal for ImmunoTherapy of Cancer
Volume number 9
Issue number 7
Article ID e002459
Start page 1
End page 14
Total pages 14
Publisher BMJ
Place of publication London, Eng.
Publication date 2021-07
ISSN 2051-1426
2051-1426
Keyword(s) ANTITUMOR-ACTIVITY
BRAF INHIBITION
clinical trials as topic
COLON-CANCER
combination
drug therapy
Immunology
immunotherapy
IPILIMUMAB
Life Sciences & Biomedicine
Oncology
PHASE-II
RAF INHIBITION
RESISTANCE
Science & Technology
T-CELL
TEMOZOLOMIDE
VEMURAFENIB
Summary With rapid advances in our understanding of cancer, there is an expanding number of potential novel combination therapies, including novel–novel combinations. Identifying which combinations are appropriate and in which subpopulations are among the most difficult questions in medical research. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review of trials of novel–novel combination therapies involving immunotherapies or molecular targeted therapies in advanced solid tumors. A MEDLINE search was conducted using a modified Cochrane Highly Sensitive Search Strategy for published clinical trials between July 1, 2017, and June 30, 2020, in the top-ranked medical and oncology journals. Trials were evaluated according to a criterion adapted from previously published Food and Drug Administration guidance and other key considerations in designing trials of combinations. This included the presence of a strong biological rationale, the use of a new established or emerging predictive biomarker prospectively incorporated into the clinical trial design, appropriate comparator arms of monotherapy or supportive external data sources and a primary endpoint demonstrating a clinically meaningful benefit. Of 32 identified trials, there were 11 (34%) trials of the novel–novel combination of anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) therapy, and 10 (31%) trials of anti-PD-1/PD-L1 and anti-vascular endothelial growth factor (VEGF) combination therapy. 20 (62.5%) trials were phase II trials, while 12 (37.5%) were phase III trials. Most (72%) trials lacked significant preclinical evidence supporting the development of the combination in the given indication. A majority of trials (69%) were conducted in biomarker unselected populations or used pre-existing biomarkers within the given indication for patient selection. Most studies (66%) were considered to have appropriate comparator arms or had supportive external data sources such as prior studies of monotherapy. All studies were evaluated as selecting a clinically meaningful primary endpoint. In conclusion, designing trials to evaluate novel–novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design. Designing trials to evaluate novel–novel combination therapies presents numerous challenges to demonstrate efficacy in a comprehensive manner. A greater understanding of biological rationale for combinations and incorporating predictive biomarkers may improve effective evaluation of combination therapies. Innovative statistical methods and increasing use of external data to support combination approaches are potential strategies that may improve the efficiency of trial design
Language eng
DOI 10.1136/jitc-2021-002459
HERDC Research category C1 Refereed article in a scholarly journal
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30153658

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.