Willemien van de Water1, Mandy Kiderlen, Esther Bastiaannet, Sabine Siesling, Rudi G J Westendorp, Cornelis J H van de Velde, Johan W R Nortier, Caroline Seynaeve, Anton J M de Craen, Gerrit-Jan Liefers. 1. Affiliations of authors: Department of Surgical Oncology (WvdW, MK, EB, CJHvdV, GJL), Department of Gerontology and Geriatrics (WvdW, MK, EB, RGJW, AJMdC), and Department of Medical Oncology (JWRN), Leiden University Medical Center, Leiden, the Netherlands; Department of Research, Comprehensive Cancer Centre the Netherlands, Utrecht, the Netherlands (SS); Department of Health Technology and Services Research, University of Twente, Enschede, the Netherlands (SS); Department of Medical Oncology, Erasmus MC-Daniel Den Hoed Cancer Center, Rotterdam, the Netherlands (CS).
Abstract
BACKGROUND: Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients. METHODS: We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen ExemestaneAdjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor-positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65-74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided. RESULTS: Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population. CONCLUSIONS:Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.
RCT Entities:
BACKGROUND: Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancerpatients. METHODS: We compared characteristics and outcomes of breast cancerpatients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancerpatients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor-positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65-74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided. RESULTS: Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population. CONCLUSIONS:Breast cancer trial participants aged 75 years or older do not represent elderly breast cancerpatients of corresponding age from the general population, which hampers the external validity of a trial.
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Authors: Anna Z de Boer; Heleen C van der Hulst; Nienke A de Glas; Perla J Marang-van de Mheen; Sabine Siesling; Linda de Munck; Kelly M de Ligt; Johanneke E A Portielje; Esther Bastiaannet; Gerrit Jan Liefers Journal: Oncologist Date: 2019-09-12
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Authors: Marloes G M Derks; Nienke A de Glas; Esther Bastiaannet; Anton J M de Craen; Johanneke E A Portielje; Cornelis J H van de Velde; Floor E van Leeuwen; Gerrit-Jan Liefers Journal: Oncologist Date: 2016-07-01