ArticleJournal of the National Cancer Institute2015
Milestone Survival: A Potential Intermediate Endpoint for Immune Checkpoint Inhibitors.
Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 10 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
47 citing papers in PubMed, 10 syntheses or guidelines pooled it.
- Evolution of clinical benefit in cancer trials: comparing pivotal approval data with updated efficacy.Frontiers in public health · 2026Pooled it
- Delayed Separation of Kaplan-Meier Curves is Commonly Observed in Studies of Advanced/Metastatic Solid Tumors Treated with Anti-PD-(L)1 Therapy: Systematic Review and Meta-Analysis.Targeted oncology · 2025Pooled it
- Beyond hazard ratios: appropriate statistical methods for quantifying the clinical effectiveness of immune-oncology therapies - the example of the Netherlands.BMC medical research methodology · 2024Pooled it
- Surrogacy of one-year survival for overall survival in advanced hepatocellular carcinoma.BMC cancer · 2024Pooled it
- Efficacy of PD-1/PD-L1 inhibitors in gastric or gastro-oesophageal junction cancer based on clinical characteristics: a meta-analysis.BMC cancer · 2023Pooled it
- Assessment of Treatment Effects and Long-term Benefits in Immune Checkpoint Inhibitor Trials Using the Flexible Parametric Cure Model: A Systematic Review.JAMA network open · 2021Pooled it
- Consideration of Surrogate Endpoints for Overall Survival Associated With First-Line Immunotherapy in Extensive-Stage Small Cell Lung Cancer.Frontiers in oncology · 2021Pooled it
- Correlation of Milestone Restricted Mean Survival Time Ratio With Overall Survival Hazard Ratio in Randomized Clinical Trials of Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.JAMA network open · 2019Pooled it
- Defining the Most Appropriate Primary End Point in Phase 2 Trials of Immune Checkpoint Inhibitors for Advanced Solid Cancers: A Systematic Review and Meta-analysis.JAMA oncology · 2018Pooled it
- Milestone Analyses of Immune Checkpoint Inhibitors, Targeted Therapy, and Conventional Therapy in Metastatic Non-Small Cell Lung Cancer Trials: A Meta-analysis.JAMA oncology · 2017Pooled it
- Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial.Nature communications · 2024Trial
- Group Sequential Sample Size for Comparing Two Survival Probabilities at a Specific Time Point.Statistics in medicine · 2026Article
- AI-based tumor and organ volumetry predicts early progression after Y-90 radioembolization in liver-dominant metastatic disease.European journal of nuclear medicine and molecular imaging · 2026Article
- Causal Inference for First Non-Fatal Events With the Competing Risk of Death: A Principal Stratification Approach.Statistics in medicine · 2025Article
- 5-year real-world outcomes with first-line pembrolizumab plus chemotherapy in advanced/metastatic NSCLC.Immunotherapy · 2025Article
- Avoiding Delays in Reporting Time-to-Event Randomized Trials: Calendar Backstops and Other Approaches.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Oncolytic adenovirus encoding decorin and CD40 ligand inhibits tumor growth and liver metastasis via immune activation in murine colorectal tumor model.Molecular biomedicine · 2024Article
- Immune checkpoint inhibition (ICI) in current systemic therapies for hepatocellular carcinoma (HCC).ESMO gastrointestinal oncology · 2023Review
- Review
- Intermediate endpoints as surrogates for outcomes in cancer immunotherapy: a systematic review and meta-analysis of phase 3 trials.EClinicalMedicine · 2023Article
Corrections and comments
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Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent advancements in cancer immunotherapies offer diverse strategies for cancer treatment. Among the most promising approaches is the blockade of immune checkpoint molecules to activate antitumor immunity. With targeted immunotherapies of new mechanisms of action come greater challenges in study design and statistical analysis, as well as the need for refining clinical trial endpoints. The long-term survival and delayed clinical effects demonstrated by these therapies could result in substantial prolongation of study duration and loss of statistical power if these key attributes are not accounted for in the study design and statistical analyses. In the Brookings Conference on Clinical Cancer Research held in Washington, DC, in November 2013, several intermediate clinical endpoints, including milestone overall survival, were proposed for the evaluation of cancer immunotherapies to take into account the possibility of delayed treatment effect and to better characterize the clinical activity profile of such agents, particularly immune checkpoint inhibitors. In this manuscript, the use of milestone survival is described as a potential efficacy endpoint for immune checkpoint inhibitors in late-stage drug development that could potentially mitigate the challenge of accelerating the drug development process when the strength of this class of agents is derived from long-term follow-up.
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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.