A pilot study of atrovastatin +/- aspirin (ASA) chemoprevention in patients (pts) with Lynch Syndrome (LS): Recruitment, retention, adherence, and acceptability.

Abstract

98 Background: Pts w/LS have high lifetime risk of colorectal cancer (CRC). Intensive colonoscopy surveillance is standard in LS, but recent guideline updates have de-escalated screening intervals and favor segmental over total colectomy for LS pts w/CRC, increasing risk of interval cancers (CAs) and more advanced CAs at diagnosis. Retrospective studies have linked statin use to reduced risk of CRC. Preclinical data from our team identified lower incidence of intestinal polyps in mice exposed to Atorva+/-ASA especially when exposure preceded any neoplasia. Based on these findings, we initiated a two-arm trial to examine metabolic, epithelial and molecular impact of Atorva+/-ASA in pts w/LS. Effective recruitment, retention, adherence, and acceptability are critical to research. Methods: Pts w/LS were identified via the Fox Chase Cancer Center (FCCC) Risk Assessment Program (RAP) registry. Pts had a germline mutation in MLH1, MSH2, MSH6, PMS2, or EPCAM and were undergoing screening colonoscopy at FCCC. This was a non-randomized 2-arm trial: after biosample (blood) and baseline colonoscopy w/biopsy, pts w/hx of adenoma or CRC were enrolled on Arm B (Atorva 20 mg+ASA 325 mg x 6 wks), while those with no neoplasia hx were enrolled on Arm A (Atorva 20 mg monotherapy x 6 wks). A follow-up sigmoidoscopy was conducted at 6 wks. Adherence was determined by self-report and medication count. Acceptability was measured on a 7-point Likert scale. The study was IRB approved 18-1039. Results: From N=420 total subjects, 168 were ineligible for the study, 111 actively refused, and 76 passively refused. 65 pts consented to the study, and 66% (43/65) completed all components. 13/65 pts were removed from study before starting the intervention [5/13 w/new CA diagnosis; 7/13 w/study non-compliance;1/13 w/ineligibility], while 9/65 additional were removed after starting drug [6/9 consent withdrawal w/side effects;1/9 w/medical reason; 2/9 removed w/non-compliance]. 20 pts completed Arm A and 23 pts completed Arm B. Adherence to ASA (Arm B) and Atrova doses (Arms A&B) and acceptability ratings were both high [>90% pts met ≥80% dose adherence; mean acceptability was 1.46, range 0.31-2.39]. Conclusions: Drug adherence and study acceptability were favorable in pts who completed the study. Future analyses will assess biomarkers at the tissue and molecular level. Clinical trial information: NCT04379999 . Arm, medication, % doses adherent % pts Arm A  Atorva   100% 88%   80-99% 12% Arm B  Atorva   100% 65%   80-99% 31%   <80% 4% ASA  100% 73%  80-99% 18%  <80% 9% Acceptability (def yes=1, def no=7) Mean (SD) Do you feel participating in the study had a positive impact on your CA care? 2.39 (1.82) Do you regret that you chose to participate? (reverse scored) 0.31 (0.95) Would you recommend this study to other pts? 1.36 (0.63) Please rate your interest in participating in a future study if it involved taking ASA or Atorva for 1 year? 2.15 (1.23)