Relationship between statin use and colon cancer recurrence and survival: results from CALGB 89803

Abstract

Background: Although preclinical and epidemiological data suggest that statins may have antineoplastic properties, the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown.

Methods: We conducted a prospective observational study of 842 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival. Disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status (n = 394), and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables. All statistical tests were two-sided.

Results: Among 842 patients, 134 (15.9%) reported statin use after completing adjuvant chemotherapy. DFS among statin users and nonusers was similar (hazard ratio [HR] of cancer recurrence or death = 1.04, 95% confidence interval [CI] = 0.73 to 1.49). RFS and OS were also similar between statin users and nonusers (adjusted HR of cancer recurrence = 1.14, 95% CI = 0.77 to 1.69; adjusted HR of death = 1.15, 95% CI = 0.77 to 1.71). Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis (P(trend) = .63, .63, and .59 for DFS, RFS, and OS, respectively). The impact of statin use did not differ by tumor KRAS mutation status, with similar DFS, RFS, and OS for statin use among mutant and wild-type subgroups (P(interaction) = .84, .67, and .98 for DFS, RFS, and OS, respectively).

Conclusion: Statin use during and after adjuvant chemotherapy was not associated with improved DFS, RFS, or OS in patients with stage III colon cancer, regardless of KRAS mutation status.

Figure 1

Flow chart of patient selection from the Cancer and Leukemia Group B (CALGB) trial 89803 for inclusion in the study cohort. Q1 = Questionnaire 1, Q2 = Questionnaire 2.

Figure 2

Survival outcomes of statin users and nonusers from the Cancer and Leukemia Group B (CALGB) trial 89803. Kaplan–Meier curves of A) disease-free survival and B) overall survival of patients (n = 842) after a median follow-up of 6.5 years. Error bars represent 95% confidence intervals. Statistical significance was measured by the log-rank test. All P values were two-sided.

Figure 3

Survival outcomes of statin users and nonusers from the Cancer and Leukemia Group B (CALGB) trial 89803 stratified by KRAS mutation status. Kaplan–Meier curves of A) disease-free survival in KRAS wild-type patients, B) disease-free survival in KRAS mutant patients, C) overall survival in KRAS wild-type patients, and D) overall survival in KRAS mutant patients in those with tissue available for KRAS mutation testing (n = 394) after a median follow-up of 6.5 years. Error bars represent 95% confidence intervals. Statistical significance was measured by the log-rank test. All P values were two-sided.

Figure 4

Risk of cancer recurrence and death among statin users and nonusers across strata of predictors of cancer outcome. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer recurrence and death (disease-free survival) were calculated by Cox proportional hazards regression models. Wald test of cross-product terms was used to calculate P_interaction and was two-sided. ASA = aspirin; BMI = body mass index; ECOG = Eastern Cooperative Oncology Group; IFL = irinotecan, bolus 5-FU, LV; MET = metabolic equivalent task; PS = performance status; T = depth of invasion through bowel wall; 5-FU/LV = bolus 5-fluorouracil/leucovorin; .