Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis
Objective Disease-free survival (DFS) is frequently used as the primary endpoint in trials of adjuvant and neoadjuvant therapies for early-stage pancreatic cancer (PC), but its validity as a surrogate for overall survival (OS) remains uncertain. This study evaluates the strength and consistency of D...
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| Format: | Article |
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BMJ Publishing Group
2025-05-01
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| Series: | BMJ Oncology |
| Online Access: | https://bmjoncology.bmj.com/content/4/1/e000766.full |
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| author | Bishal Gyawali Luís Felipe Leite Luiz F Costa de Almeida Lucas Diniz da Conceição Mariana Macambira Noronha Marcos Belotto Erick F Saldanha Thais Baccili Cury Megid Renata D’Alpino Peixoto |
| author_facet | Bishal Gyawali Luís Felipe Leite Luiz F Costa de Almeida Lucas Diniz da Conceição Mariana Macambira Noronha Marcos Belotto Erick F Saldanha Thais Baccili Cury Megid Renata D’Alpino Peixoto |
| author_sort | Bishal Gyawali |
| collection | DOAJ |
| description | Objective Disease-free survival (DFS) is frequently used as the primary endpoint in trials of adjuvant and neoadjuvant therapies for early-stage pancreatic cancer (PC), but its validity as a surrogate for overall survival (OS) remains uncertain. This study evaluates the strength and consistency of DFS as a surrogate for OS in early-stage PC trials.Methods and analysis This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Trials of early-stage PC involving drug therapy were identified through PubMed, Embase and Cochrane CENTRAL databases, and data on DFS and OS with HR and CIs were extracted. Trial-level surrogacy of DFS for OS was assessed using weighted linear regression, calculating the coefficient of determination (R²) and surrogate threshold effect (STE).Results 29 trials involving 6777 patients were included. In adjuvant trials, HR of DFS strongly correlated with HR of OS (R²=0.70) at trial-level, with the STE of 0.94 indicating the maximum DFS HR beyond which OS benefit was unlikely. The correlation strength differed between phase III (R²=0.71) versus phase II (R²=0.67) trials. This correlation was stronger in trials including radiation therapy (R²=0.81) and trials in the neoadjuvant setting (R²=0.90). No trial in our study was a registration trial of a new molecule and all involved chemotherapy.Conclusion Treatment effects on DFS had a strong correlation with treatment effects on OS, making DFS a potential surrogate endpoint for OS in early-stage PC trials of cytotoxic chemotherapies, but its use in registration trials requires careful consideration due to variability across treatment settings and trial designs.PROSPERO registration number CRD42024595441. |
| format | Article |
| id | doaj-art-ced64efe2bfc4bacbeb753ef702628b2 |
| institution | OA Journals |
| issn | 2752-7948 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Oncology |
| spelling | doaj-art-ced64efe2bfc4bacbeb753ef702628b22025-08-20T02:16:03ZengBMJ Publishing GroupBMJ Oncology2752-79482025-05-014110.1136/bmjonc-2025-000766Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysisBishal Gyawali0Luís Felipe Leite1Luiz F Costa de Almeida2Lucas Diniz da Conceição3Mariana Macambira Noronha4Marcos Belotto5Erick F Saldanha6Thais Baccili Cury Megid7Renata D’Alpino Peixoto8fellow and assistant professor of public health sciencesDepartment of Medical Sciences, Federal Fluminense University, Niterói, BrazilDepartment of Medical Sciences, Federal Fluminense University, Niterói, BrazilDepartment of Medical Sciences, Federal Fluminense University, Niterói, BrazilDepartment of Medical Oncology, Universidade Federal do Ceará, Fortaleza, BrazilDepartment of Surgical Oncology, Hospital 9 de Julho, São Paulo, BrazilDivision of Medical Oncology and Haematology, Department of Medicine, Princess Margaret Hospital Cancer Centre, University of Toronto, Toronto, Ontario, CanadaDr Georges-L-Dumont University Hospital Centre, Moncton, New Brunswick, CanadaDepartment of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia, CanadaObjective Disease-free survival (DFS) is frequently used as the primary endpoint in trials of adjuvant and neoadjuvant therapies for early-stage pancreatic cancer (PC), but its validity as a surrogate for overall survival (OS) remains uncertain. This study evaluates the strength and consistency of DFS as a surrogate for OS in early-stage PC trials.Methods and analysis This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Trials of early-stage PC involving drug therapy were identified through PubMed, Embase and Cochrane CENTRAL databases, and data on DFS and OS with HR and CIs were extracted. Trial-level surrogacy of DFS for OS was assessed using weighted linear regression, calculating the coefficient of determination (R²) and surrogate threshold effect (STE).Results 29 trials involving 6777 patients were included. In adjuvant trials, HR of DFS strongly correlated with HR of OS (R²=0.70) at trial-level, with the STE of 0.94 indicating the maximum DFS HR beyond which OS benefit was unlikely. The correlation strength differed between phase III (R²=0.71) versus phase II (R²=0.67) trials. This correlation was stronger in trials including radiation therapy (R²=0.81) and trials in the neoadjuvant setting (R²=0.90). No trial in our study was a registration trial of a new molecule and all involved chemotherapy.Conclusion Treatment effects on DFS had a strong correlation with treatment effects on OS, making DFS a potential surrogate endpoint for OS in early-stage PC trials of cytotoxic chemotherapies, but its use in registration trials requires careful consideration due to variability across treatment settings and trial designs.PROSPERO registration number CRD42024595441.https://bmjoncology.bmj.com/content/4/1/e000766.full |
| spellingShingle | Bishal Gyawali Luís Felipe Leite Luiz F Costa de Almeida Lucas Diniz da Conceição Mariana Macambira Noronha Marcos Belotto Erick F Saldanha Thais Baccili Cury Megid Renata D’Alpino Peixoto Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis BMJ Oncology |
| title | Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis |
| title_full | Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis |
| title_fullStr | Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis |
| title_full_unstemmed | Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis |
| title_short | Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis |
| title_sort | disease free survival as a surrogate for overall survival in early stage pancreatic cancer trials a correlation meta analysis |
| url | https://bmjoncology.bmj.com/content/4/1/e000766.full |
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