ReviewClinical cancer research : an official journal of the American Association for Cancer Research2018
Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors.
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
26 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Impact of open-label versus blinded study design on patient-reported outcomes data in randomized clinical trials of immunotherapy in advanced or metastatic cancer patients: a systematic review.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2022Pooled it
- Efficacy and safety of anticancer drug combinations: a meta-analysis of randomized trials with a focus on immunotherapeutics and gene-targeted compounds.Oncoimmunology · 2020Pooled it
- Ten challenges and opportunities in computational immuno-oncology.Journal for immunotherapy of cancer · 2024Review
- FDA regulatory considerations for oncology drug development.Pharmacology research & perspectives · 2024Article
- Realizing the promise of Project Optimus: Challenges and emerging opportunities for dose optimization in oncology drug development.CPT: pharmacometrics & systems pharmacology · 2024Review
- The transcriptomic expression pattern of immune checkpoints shows heterogeneity between and within cancer types.American journal of cancer research · 2024Article
- T-cell priming transcriptomic markers: implications of immunome heterogeneity for precision immunotherapy.NPJ genomic medicine · 2023Article
- Detection and evaluation of signals for immune-related adverse events: a nationwide, population-based study.Frontiers in oncology · 2023Article
- Prognostic value of immunotherapy-induced organ inflammation assessed onEuropean journal of nuclear medicine and molecular imaging · 2022Article
- Article
- When Less May Be Enough: Dose Selection Strategies for Immune Checkpoint Inhibitors Focusing on AntiPD-(L)1 Agents.Targeted oncology · 2022Review
- Melanoma: An immunotherapy journey from bench to bedside.Cancer treatment and research · 2022Article
- Metronomic Chemotherapy Modulates Clonal Interactions to Prevent Drug Resistance in Non-Small Cell Lung Cancer.Cancers · 2021Article
- The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker.Cancer cell · 2021Review
- Recent Progress in the Synergistic Combination of Nanoparticle-Mediated Hyperthermia and Immunotherapy for Treatment of Cancer.Advanced healthcare materials · 2021Review
- Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response.British journal of clinical pharmacology · 2020Review
- Spectrum and Clinical Activity of PD-1/PD-L1 Inhibitors: Regulatory Approval and Under Development.Current oncology reports · 2020Review
- Relationship between protein biomarkers of chemotherapy response and microsatellite status, tumor mutational burden and PD-L1 expression in cancer patients.International journal of cancer · 2020Article
- Combined Anti-Cancer Strategies Based on Anti-Checkpoint Inhibitor Antibodies.Antibodies (Basel, Switzerland) · 2020Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified.
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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.