SynthesisOncoimmunology2020
Efficacy and safety of anticancer drug combinations: a meta-analysis of randomized trials with a focus on immunotherapeutics and gene-targeted compounds.
Synthesis in Oncoimmunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) N-of-1 Precision Oncology Study: Molecular Profiling to Match Individually Dosed, Personalized Drug Combinations.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Observational
- Physical activity decreases cancer burden by alleviating immunosenescence-related inflammation and improving overall immunity.Cell reports. Medicine · 2025Article
- Evaluation of efficacy and safety of targeted therapy and immune checkpoint inhibitors in metastatic colorectal cancer.World journal of gastrointestinal oncology · 2025Article
- Synergistic effects of abietic acid combined with doxorubicin on apoptosis induction in a human colorectal cancer cell line.Scientific reports · 2025Article
- Review
- Cancer Cell's Achilles Heels: Considerations for Design of Anti-Cancer Drug Combinations.International journal of molecular sciences · 2024Article
- A pan-cancer screen identifies drug combination benefit in cancer cell lines at the individual and population level.Cell reports. Medicine · 2024Article
- Disrupting cellular memory to overcome drug resistance.Nature communications · 2023Article
- SYNDEEP: a deep learning approach for the prediction of cancer drugs synergy.Scientific reports · 2023Article
- 3D collagen microchamber arrays for combined chemotherapy effect evaluation on cancer cell numbers and migration.Biomicrofluidics · 2023Article
- MG-International journal of molecular sciences · 2022Article
- Challenges of applying multicellular tumor spheroids in preclinical phase.Cancer cell international · 2021Review
- Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations.International journal of molecular sciences · 2021Article
- Open peer review commentary on building clinically relevant outcomes across the Alzheimer's disease spectrum.Alzheimer's & dementia (New York, N. Y.) · 2021Article
- Pharmacogenomics of Impaired Tyrosine Kinase Inhibitor Response: Lessons Learned From Chronic Myelogenous Leukemia.Frontiers in pharmacology · 2021Review
- Novel clinical trial designs emerging from the molecular reclassification of cancer.CA: a cancer journal for cliniciansReview
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Hundreds of trials are being conducted to evaluate combination of newer targeted drugs as well as immunotherapy. Our aim was to compare efficacy and safety of combination versus single non-cytotoxic anticancer agents. We searched PubMed (01/01/2001 to 03/06/2018) (and, for immunotherapy, ASCO and ESMO abstracts (2016 through March 2018)) for randomized clinical trials that compared a single non-cytotoxic agent (targeted, hormonal, or immunotherapy) versus a combination with another non-cytotoxic partner. Efficacy and safety endpoints were evaluated in a meta-analysis using a linear mixed-effects model (guidelines per PRISMA Report).We included 95 randomized comparisons (single vs. combination non-cytotoxic therapies) (59.4%, phase II; 41.6%, phase III trials) (29,175 patients (solid tumors)). Combinations most frequently included a hormonal agent and a targeted small molecule (23%). Compared to single non-cytotoxic agents, adding another non-cytotoxic drug increased response rate (odds ratio [OR]=1.61, 95%CI 1.40-1.84)and prolonged progression-free survival (hazard ratio [HR]=0.75, 95%CI 0.69-0.81)and overall survival (HR=0.87, 95%CI 0.81-0.94) (all p<0.001), which was most pronounced for the association between immunotherapy combinations and longer survival. Combinations also significantlyincreased the risk of high-grade toxicities (OR=2.42, 95%CI 1.98-2.97) (most notably for immunotherapy and small molecule inhibitors) and mortality at least possibly therapy related (OR: 1.33, 95%CI 1.15-1.53) (both p<0.001) (absolute mortality = 0.90% (single agent) versus 1.31% (combinations)) compared to single agents. In conclusion, combinations of non-cytotoxic drugs versus monotherapy in randomized cancer clinical trials attenuated safety, but increased efficacy, with the balance tilting in favor of combination therapy, based on the prolongation in survival.
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Registered trials
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