ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Predictable Clinical Benefits without Evidence of Synergy in Trials of Combination Therapies with Immune-Checkpoint Inhibitors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- Immunotherapy checkpoint inhibitor-combination therapy versus chemotherapy alone among Chinese population in cholangiocarcinoma treatment: a systematic review and meta-analysis.European journal of clinical pharmacology · 2026Pooled it
- Longitudinal changes in the relative toxicity of FDA-approved oncology therapeutics: evidence from paired initial and updated RCT reports.Frontiers in public health · 2026Pooled it
- Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft-tissue Sarcomas: Clinical Outcomes and Biological Correlates.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.Nature communications · 2024Trial
- A novel combination therapy for ER+ breast cancer suppresses drug resistance via an evolutionary double-bind.Molecular systems biology · 2026Article
- Additivity, Not Synergy, Underlies the Efficacy of Current Combination Regimens in Urothelial Cancer.Cancer research communications · 2026Article
- Rethinking the role of synergy calculations in the next century of drug combination discovery.Med (New York, N.Y.) · 2026Review
- Immunotherapy rechallenge in gastric cancer: resistance mechanisms, molecular stratification, and precision decision-making.Frontiers in immunology · 2026Review
- Engineering of the Melanoma Inhibitor of Apoptosis (ML-IAP) Anticancer Peptide Through Comprehensive In Silico Approaches.Human mutation · 2026Article
- CDK12 regulates cellular metabolism to promote glioblastoma growth.JCI insight · 2025Article
- Novel Pretreatment Autoantibodies Correlate with Enfortumab Vedotin-Related Dermatologic Events in Patients with Advanced Urothelial Cancer.Cancer research communications · 2025Article
- Article
- Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Investigating the Synergistic Effects of Pembrolizumab and Chemotherapy in Gastric and Gastroesophageal Junction Cancer.Journal of gastric cancer · 2025Article
- A Model of Intratumor and Interpatient Heterogeneity Explains Clinical Trials of Curative Combination Therapy for Lymphoma.Blood cancer discovery · 2025Article
- Twist1 Regulates the Immune Checkpoint VISTA and Promotes the Proliferation, Migration and Progression of Pancreatic Cancer Cells.Journal of cellular and molecular medicine · 2025Article
- Investigating the synergistic effects of immunochemotherapy in esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2025Article
- Clinical and experimental treatment of advanced melanoma with a focus on immunotherapy.Clinical and experimental immunology · 2025Review
- Article
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCombinations of immune-checkpoint inhibitors (ICI) with other cancer therapies have been approved for advanced cancers in multiple indications, and numerous trials are under way to test new combinations. However, the mechanisms that account for the superiority of approved ICI combinations relative to their constituent monotherapies remain unknown. EXPERIMENTAL
designWe analyzed 13 phase III clinical trials testing combinations of ICIs with each other or other drugs in patients with advanced melanoma and lung, breast, gastric, kidney, and head and neck cancers. The clinical activity of the individual constituent therapies, measured in the same or a closely matched trial cohort, was used to compute progression-free survival (PFS) curves expected under a model of independent drug action. To identify additive or synergistic efficacy, PFS expected under this null model was compared with observed PFS by Cox regression.
resultsPFS elicited by approved combination therapies with ICIs could be accurately predicted from monotherapy data using the independent drug action model (Pearson
conclusionsCombining ICIs with other cancer therapies affords predictable and clinically meaningful benefit by providing patients with multiple chances of response to a single agent. Conversely, there exists no evidence in phase III trials that other therapies interact with and enhance the activity of ICIs. These findings can inform the design and testing of new ICI combination therapies while emphasizing the importance of developing better predictors (biomarkers) of ICI response.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.