Abstract P4-18-01: Do participants in adjuvant breast cancer trials reflect the breast cancer patient population?
Authors: Thompson Alastair M , Dryden Ruth , McCowan Colin , Harrow Alison , Treweek Shaun 
Published: May 2015

Abstract
Background: To be clinically relevant, randomised clinical trials need to involve participants who reflect those in the community likely to receive the treatments under evaluation. However, as few as 5% of patients with chronic medical illnesses (asthma, diabetes) are documented as meeting therapeutic trial entry criteria. This study examined a population based cohort of women diagnosed with early breast cancer to compare the eligibility criteria of 12 influential adjuvant endocrine therapy, chemotherapy or radiotherapy trials with clinical eligibility and actual treatment at a single regional cancer centre.
Methods: 421 Phase III trials of adjuvant endocrine therapy, chemotherapy or radiotherapy treatment for early breast cancer referenced in 5 recent national guidelines were identified and shortlisted by breast cancer specialists of multiple disciplines at a national meeting to identify the twelve most influential trials: 5 endocrine (ATAC, BIG 1-98, IES, MA17, TEAM), 2 chemotherapy (NSABP B-28, TACT) and 5 radiotherapy trials (Whelan et al JNCI 2002, EORTC Bartelink NEJM 2001, START A, START B, TARGIT-A). Eligibility criteria were extracted from protocols and subsequently applied to a 16-year (1993 – 2008) community-based cohort of 4811 women who had received a diagnosis of breast cancer, with the proportion who met each criterion calculated. HER2 therapy trials were excluded since the cohort did not have HER2 testing prior to 2000. Clinical guideline-based criteria for the adjuvant treatments described within each trial were also applied to the cohort. Finally, the proportion of women actually prescribed adjuvant endocrine therapy meeting the relevant trial eligibility criteria, taking account of drug availability, was calculated using linkage to community pharmacy records.
Results: Of 4811 women in the cohort, 3535 (73%) were eligible for at least one trial. Eligibility ranged from 34% (1653 women) for the chemotherapy trials, through 47% (2247) for at least one endocrine therapy trial, to 71% (3419) for a radiotherapy trial.
The proportion of women considered clinically eligible for the same treatment, was greater (MA17, Whelan et al JNCI 2002, TACT), similar (BIG1-98, IES, NSABP B-28) or less than (ATAC, EORTC Bartelink NEJM 2001, START A and B trials, TARGIT A) trial eligibility criteria, with no consistent pattern of exclusion. It was rare for more than 45% of women of the community cohort to be eligible for a given trial. The proportion of women who actually received an endocrine therapy in clinical practice, but would not have been eligible for the trial evaluating that therapy (ATAC, BIG 1-98, IES and MA17), ranged from 44% to 83%.
Interpretation: Trial entry criteria for early breast cancer are reassuringly more inclusive for adjuvant breast cancer treatments than for chronic medical conditions. However, the application of trial evidence in the clinic may be at variance with the trials and, for adjuvant endocrine therapy at least, a substantial proportion of women receive therapy who would not have been eligible for the relevant trial.
Citation Format: Alastair M Thompson, Ruth Dryden, Colin McCowan, Alison Harrow, Shaun Treweek. Do participants in adjuvant breast cancer trials reflect the breast cancer patient population? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-18-01.