1. Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists
- Author
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Nicolas Methy, Franck Bonnetain, Laurent Bedenne, BMC, Ed., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre d'épidémiologie des populations ( CEP ), and Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL )
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Oncology ,Cancer Research ,Time Factors ,Digestive System Neoplasms ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,0302 clinical medicine ,Quality of life ,Surveys and Questionnaires ,Medicine ,030212 general & internal medicine ,MESH: Treatment Outcome ,Response rate (survey) ,MESH : Evidence-Based Medicine ,Clinical Trials as Topic ,Evidence-Based Medicine ,MESH: Endpoint Determination ,MESH: Research Design ,MESH : Questionnaires ,MESH : Research Design ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,MESH: Reproducibility of Results ,medicine.anatomical_structure ,Treatment Outcome ,Research Design ,030220 oncology & carcinogenesis ,Data Interpretation, Statistical ,MESH: Survival Analysis ,MESH : Disease-Free Survival ,MESH : Endpoint Determination ,France ,MESH : Time Factors ,Research Article ,medicine.medical_specialty ,MESH: Clinical Trials as Topic ,Endpoint Determination ,Rectum ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MESH : Treatment Outcome ,lcsh:RC254-282 ,Disease-Free Survival ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,Genetics ,Humans ,MESH : Data Interpretation, Statistical ,MESH : France ,Survival analysis ,MESH: Humans ,business.industry ,Surrogate endpoint ,MESH: Digestive System Neoplasms ,MESH : Reproducibility of Results ,MESH: Questionnaires ,MESH : Humans ,MESH: Time Factors ,Cancer ,Reproducibility of Results ,MESH: Quality of Life ,MESH : Quality of Life ,medicine.disease ,Survival Analysis ,MESH : Clinical Trials as Topic ,MESH: France ,Localized disease ,MESH: Disease-Free Survival ,Quality of Life ,MESH : Digestive System Neoplasms ,MESH : Survival Analysis ,business ,MESH: Data Interpretation, Statistical ,MESH: Evidence-Based Medicine - Abstract
Background Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL). Methods In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion. Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking. Results Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS. DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations. Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed. Conclusion The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.
- Published
- 2010
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