Early endpoints, such as progression-free survival (PFS), are increasingly used as surrogates for overall survival (OS) to accelerate approval of novel oncology agents. Compiling trial-level data from randomized controlled trials (RCTs) could help to develop a predictive framework to ascertain correlation trends between treatment effects for early and late endpoints. Through trial-level correlation and random-effects meta-regression analysis, we assessed the relationship between hazard ratio (HR) OS and (1) HR PFS and (2) odds ratio (OR) PFS at 4 and 6 months, stratified according to the mechanism of action of the investigational product. Using multiple source databases, we compiled a data set including 81 phase II-IV RCTs (35 drugs and 156 observations) of patients with non-small-cell lung cancer. Low-to-moderate correlations were generally observed between treatment effects for early endpoints (based on PFS) and HR OS across trials of agents with different mechanisms of action. Moderate correlations were seen between treatment effects for HR PFS and HR OS across all trials, and in the programmed cell death-1/programmed cell death ligand-1 and epidermal growth factor receptor trial subsets. Although these results constitute an important step, caution is advised, as there are some limitations to our evaluation, and an additional patient-level analysis would be needed to establish true surrogacy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351517 | PMC |
| http://dx.doi.org/10.3389/fonc.2021.672916 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP): Study Protocol and Rationale.
Int J Stroke
January 2025
Department of Neurosurgery and Interventional Neuroradiology, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, 45 Changchun St, Beijing 100053, China.
Rationale: The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.
Aims: This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.
An Open-Label Pilot Study to Examine the Safety, Tolerability and Efficacy of Deutetrabenazine in Isolated Dystonia.
Mov Disord Clin Pract
January 2025
Parkinson Disease and Movement Disorders Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Background: Dystonia may respond to VMAT2 inhibition.
Objectives: Providing pilot data on the safety, tolerability, and efficacy of deutetrabenazine in non dopa-responsive dystonia.
Methods: Deutetrabenazine was titrated by adults with isolated dystonia.
A randomized controlled trial to assess the efficacy of standardized tai chi in prefrail older adults with immunosenescence: design and protocol.
BMC Complement Med Ther
January 2025
Geriatric department, Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu, 610072, Sichuan, China.
Background: Frailty is a common geriatric syndrome worldwide, and its early identification and intervention have important clinical significance. Resistance training has been recommended as an efficient means to combat loss of muscle strength and mass; however, it is often not a prioritized option for older adults. Tai chi is a well-known traditional Chinese exercise that has a beneficial impact on physical performance, balance ability, metabolism, and immune function.
View Article and Find Full Text PDFDeeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial.
Nat Commun
January 2025
Center for Early Detection and Interception of Blood Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.
View Article and Find Full Text PDFNuclear Cardiology Surrogate Biomarkers in Clinical Trials.
J Nucl Med
January 2025
Departments of Medicine (Division of Artificial Intelligence in Medicine), Imaging, and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California;
Nuclear cardiology offers a diverse range of imaging tools that provide valuable insights into myocardial perfusion, inflammation, metabolism, neuroregulation, thrombosis, and microcalcification. These techniques are crucial not only for diagnosing and managing cardiovascular conditions but also for gaining pathophysiologic insights. Surrogate biomarkers in nuclear cardiology, represented by detectable imaging changes, correlate with disease processes or therapeutic responses and can serve as endpoints in clinical trials when they demonstrate a clear link with these processes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!