Abstract | BACKGROUND: Overall survival (OS) has traditionally been the primary end point in studies evaluating the clinical benefit of first-line chemotherapy in metastatic, locally advanced, or unresectable pancreatic cancer (MLAUPC). Given the prolonged follow-up assessment required to obtain OS and its potential to be confounded by second-line treatments, this study sought to determine whether progression-free survival (PFS), response rate (RR), or disease control rate (DCR) can serve as a reliable surrogate for OS. METHODS: A systematic review and meta-analysis was performed including all phase 3 clinical trials for MLAUPC, with gemcitabine as the control arm of the trial. The hazard ratios (HRs) for OS and PFS and odds ratios ( ORs) for RR and DCR were recorded. A weighted Pearson correlation coefficient was estimated for the association between OS and the other outcomes. The primary analysis used a random effects weighting model, whereas the secondary analyses used a fixed effects- or sample size-weighted approach. RESULTS: For the study, 24 randomized controlled trials were identified. The Pearson correlation coefficient between OS and PFS was 0.86 (95% confidence interval [CI] 0.67-0.94; p < 0.001). Sensitivity analysis of the studies with little to no crossover further showed a correlation coefficient of 0.91 (95% CI 0.76-0.97; p < 0.001). The correlation coefficient between OS and RR was 0.45 (95% CI 0.07-0.72; p = 0.02) and between OS and DCR was 0.74 (95% CI 0.38-0.90; p < 0.001). CONCLUSIONS: First-line chemotherapy trials for MLAUPC show a robust correlation between OS and PFS, affirming its role as a surrogate of OS.
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Authors | Eleftherios A Makris, Regina MacBarb, Danielle J Harvey, George A Poultsides |
Journal | Annals of surgical oncology
(Ann Surg Oncol)
Vol. 24
Issue 8
Pg. 2371-2378
(Aug 2017)
ISSN: 1534-4681 [Electronic] United States |
PMID | 28397190
(Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
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Chemical References |
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Biomarkers
(metabolism)
- Humans
- Pancreatic Neoplasms
(drug therapy, metabolism, mortality, pathology)
- Prognosis
- Randomized Controlled Trials as Topic
- Survival Rate
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