S2111 CFTR Modulators Are Not Associated With Reduction in Cancer Incidence: A Propensity Matched Analysis of 15,280 Cystic Fibrosis Patients

Introduction: Cystic fibrosis trans membrane conductance regulator (CFTR) modulators have been shown to significantly improve the clinical outcomes and life expectancy of patients with cystic fibrosis (CF). However, the long term safety of these medications, particularly regarding to cancer risk or benefit, remains an area of ongoing investigation. We aimed to assess the long-term cancer risk and/or benefit with CFTR modulators. Methods: We conducted a retrospective cohort study in the United States using the TriNetX Research Network to identify patients with CF, then stratified into 2 groups: CF patients treated with CFTR modulators (deutivacaftor, elexacaftor, ivafactor, lumacaftor, tezacaftor and vanzacaftor) within 3 years after CF diagnosis and those who were not (controls). Cohorts were matched using 1-to-1 propensity score matching on demographics, comorbidities, family history of malignancy, social determinants, treatments, and lung transplant. Kaplan Meier analysis, and Cox regression analysis were used to assess the 10-year outcomes, including new-onset cancer, gastrointestinal or hepatobiliary cancers, all-cause mortality, and all-cause hospitalizations among CF patients using CFTR modulators compared to controls. Results: A total of 7,640 patients with CF treated with CFTR modulators were propensity matched with 7,640 controls. Among unmatched samples, patients in the treatment group were younger, White, had more men, with higher rates of malnutrition, and lower rates of smoking and family history of malignancy (all P< 0.0001). Furthermore, CF patients who received CFTR modulators were more likely to be treated with antibiotics and less likely to be on IS agents (P < 0.0001). Among matched samples, there were no significant differences in the overall risk of cancer (3.7% vs 3.9%, hazard ratio [HR] 1.028, 95% confidence interval [CI[: 0.859-1.231) and risk of gastrointestinal cancers (0.3% vs 0.2%, HR 1.684, 95% CI: 0.835-3.393); however, patients on CFTR modulators were at lower risk of 10-year mortality (1.0% vs 3.1%, HR 0.357, 95% CI: 0.277-0.461), and higher risk of all-cause hospitalization (13.0% vs 9.5%, HR 1.364, 95% CI 1.239-1.503). Conclusion: Our study showed that there is no conclusive evidence linking CFTR modulators to cancer prevention in CF patients, although their use correlated with reduced mortality, and increased healthcare resource utilization. Additional long-term prospective studies are required to further understand the association between CFTR modulators and cancer risk.