SynthesisJAMA network open2019
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.
Synthesis in JAMA network open, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 4 of them syntheses that pooled it.
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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
9 citing papers in PubMed, 4 syntheses or guidelines pooled 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
- The efficacy and safety of immunotherapy as first-line treatment for extensive-stage small cell lung cancer: evaluating based on reconstructed individual patient data.Frontiers in oncology · 2024Pooled 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
- Validation of Progression-Free Survival Rate at 6 Months and Objective Response for Estimating Overall Survival in Immune Checkpoint Inhibitor Trials: A Systematic Review and Meta-analysis.JAMA network open · 2020Pooled it
- Randomized Double-Blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Strategies to address non-proportional hazards between survival curves - Lessons from phase III trials in hepatocellular carcinoma.Journal of hepatology · 2026Article
- Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume II-practical challenges.Journal for immunotherapy of cancer · 2020Article
- Challenges of evaluating immunotherapy efficacy in solid tumors.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2019Article
- Analysis of Survival Curves: Statistical Methods Accounting for the Presence of Long-Term Survivors.Frontiers in oncology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Importance: Immune checkpoint inhibitors (ICIs) have unique patterns of response and survival that differ from conventional chemotherapies. Novel intermediate end points are urgently required to detect the early signals of ICI activity. Objective: To evaluate milestone rate (Kaplan-Meier estimates of survival probabilities at given time points) and milestone restricted mean survival time (RMST, the area under survival curves up to given time points) as potential intermediate end points for ICI trials. Data Sources: Electronic databases (pre-MEDLINE, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) were searched for randomized clinical trials published between January 1, 2000, and December 31, 2017. Study Selection: Phase 2 and phase 3 randomized clinical trials evaluating ICIs in advanced solid tumors. Data Extraction and Synthesis: Two investigators extracted the data and reconstructed individual patient data to estimate the milestone rate or milestone RMST from the published Kaplan-Meier curves. Main Outcomes and Measures: Trial-level milestone rates or milestone RMSTs were estimated for 6-month and 9-month progression-free survival (PFS) and 9-month and 12-month overall survival (OS). A weighted linear regression model evaluated the correlations of ratios of milestone rates or milestone RMSTs with OS hazard ratios (HRs). Results: Twenty-six trials examining 8 different tumor types were identified, including 12 892 patients. Overall survival HR was correlated with the ratio of 9-month OS milestone rate (R2 = 0.45; 95% CI, 0.27-0.74), and with the ratio of 12-month OS milestone rate (R2 = 0.40; 95% CI, 0.22-0.70). The ratio of 9-month OS milestone RMST (R2 = 0.60; 95% CI, 0.28-0.74) and ratio of 12-month OS milestone RMST were correlated with OS HR (R2 = 0.64; 95% CI, 0.42-0.78). No correlations were observed between OS HR and the ratio of 6-month or 9-month PFS milestone rates or milestone RMSTs. Conclusions and Relevance: Ratios of OS milestone RMSTs had a stronger correlation with OS HRs than ratios of OS milestone rates, whereas ratios of PFS milestone rates and ratios of PFS milestone RMSTs were not correlated with OS HRs. The OS milestone RMST could be further studied as an intermediate end point in future ICI trials.
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