PD-1/PD-L1 immune checkpoint blockade (ICB) has improved overall survival (OS) in solid tumor trials; however, parallel improvements in Response Evaluation Criteria in Solid Tumors (RECIST)-based surrogate end points, progression-free survival (PFS), and objective response rate (ORR), are not always observed. Here, we assess the surrogacy of PFS/ORR for OS with ICB therapy across advanced/metastatic tumors. In a trial-level analysis (N = 40 randomized trials), PFS, ORR, and OS treatment effects were correlated (Spearman's rho). In a patient-level analysis, data were extracted from available trials of durvalumab; the correlation of PFS and OS was evaluated (Bayesian normal-induced-copula-estimation model) and the ordinal association between objective response and OS hazard ratio (HR) were assessed with concordance index measures. High correlation was observed between PFS HR and OS HR in intention-to-treat (ITT; rho = 0.76) and PD-L1-enriched populations (0.74); modest (or limited) benefit in PFS was associated with meaningful improvement in OS. Moderate correlations were observed between ΔORR and OS HR: ITT, -0.63; PD-L1-enriched, -0.53. At the patient level, a positive association was observed between PFS and OS in non-small cell lung cancer (Kendall's Tau = 0.793; 95% confidence interval, 0.789-0.797), head and neck squamous cell carcinoma (0.794; 0.789-0.798), and bladder cancer (0.872; 0.869-0.875). Objective responders had significantly better OS (concordance index > 0.9) than nonresponders across these tumor types. Modest (or limited) improvement in RECIST-based end points did not rule out meaningful OS benefit, indicating they are imperfect surrogates and do not fully capture ICB clinical benefit. Therefore, caution is advised when basing early discontinuation of novel ICB agents on these end points.
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http://dx.doi.org/10.1002/cpt.1956 | DOI Listing |
Endocrinol Diabetes Metab
January 2025
Department of Endocrinology and Metabolism, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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View Article and Find Full Text PDFClin Rheumatol
January 2025
Department of Rheumatology, Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, People's Republic of China.
Introduction/objectives: Sjogren's syndrome (SS) is a chronic inflammatory and difficult-to-treat autoimmune disease. Timosaponin AIII (TAIII), a plant-derived steroidal saponin, effectively inhibits cell proliferation, induces apoptosis, and exhibits anti-inflammatory properties. This study explored the mechanisms of action of TAIII in SS treatment by studying gut microbiota and short-chain fatty acids (SCFAs) using fecal metabolomics.
View Article and Find Full Text PDFClin Rheumatol
January 2025
Department of Public Health, University of Murcia, Campus de Ciencias de la Salud, Murcia, 30120, Spain.
Introduction: Therapeutic drug monitoring (TDM) in inflammatory rheumatic diseases (RMDs) is gaining interest. However, there are unresolved questions about the best practices for implementing TDM effectively in clinical settings.
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Clin Rheumatol
January 2025
Department of Rheumatology and Immunology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Objectives: To investigate the clinical and laboratory features of Sjögren's syndrome-associated autoimmune liver disease (SS-ALD) patients and identify potential risk and prognostic factors.
Methods: SS patients with or without ALD, who visited Tongji Hospital between the years 2011 and 2021 and met the 2012 American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome, were retrospectively enrolled. The clinical and laboratory data of the enrolled patients, including autoimmune antibodies, were collected and analyzed with principal component analysis, correlation analysis, LASSO regression, and Cox regression.
Lasers Med Sci
January 2025
University of Campinas, Campinas, Brazil.
Purpose: RVVC is defined as four or more episodes of candidiasis in a 12-month period. Conventional treatment is complex and often involves long-term medication use or multiple treatments. ABL therapy is a promising treatment option as it is acceptable to women and has only rare side effects.
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