Abstract
Background: Immune checkpoint inhibitors (ICIs) are commonly used in the treatment of multiple types of cancer. Several small studies have identified an association between antibiotic exposure and ICI failure. Furthermore, ICI failure has also been associated with decreased tumor mutation burden (TMB), with racial disparities being noted. However, to date there are no studies that have investigated the relationship of potential racial disparities and antibiotic exposure on clinical outcomes in patients receiving ICI therapy. The purpose of our systematic review and meta-analysis is to determine the impact of antibiotic (ATB) exposure on overall survival in patients receiving ICI therapy. An additional goal is to determine if racial disparities are present. Methods: We conducted a systematic review and meta-analysis utilizing PRISMA guidance of all randomized controlled trials, or observational studies that evaluated the impact of antibiotic exposure on ICI efficacy. We excluded studies that did not report overall survival. The primary outcome of this study is overall survival (OS) among ICI patients with antibiotic exposure, compared to patients who received ICI therapy alone. Secondary outcomes include response rate (RR), and progression-free survival (PFS). An a priori subgroup analysis for the primary outcome will be conducted based on race, cancer type, and specific ICI utilized. Results: A total of twelve studies (n=1,868 patients) were included in the final analysis. Among all patients, the most common reasons for ICI use were NSCLC (n=1,180), melanoma (n=316) and RCC (n=238). Among all patients, the most commonly used ICI was anti PD-1/PD-L1 (n=708), nivolumab (n=440) and pembrolizumab (n=63). Of the total patients analyzed, 446 patients (23.9%) received ATB within 6 months surrounding ICI therapy, and 1,422 patients (76.1%) did not receive any ATB surrounding ICI therapy. No studies reported ethnicity in their published results. Patients treated with ATB had lower overall survival compared to those without antibiotic exposure (ATB- 7.5 months; No ATB- 18.9 months). RR (ATB- 14.7%; No ATB 50.9%) and PFS (ATB- 2.4 months; No ATB- 5.1 months) were also shorter. Conclusions: ATB use was associated with less overall survival compared to non-ATB use in patients receiving ICI therapy. Our findings suggest that measures to promote reduced ATB use in patients receiving ICI therapy may help to improve clinical outcomes. No studies in the final analysis reported race and ethnicity. While it is hypothesized that race and ethnicity may play a role in ICI response, further research to evaluate the role of race and ethnicity is needed, which may help clinicians to better identify patients most likely to benefit from ICI therapy.
Citation Format: Armani B Hayes, John Allen. Impact of antibiotic exposure on the overall survival in patients receiving immune checkpoint inhibitors: Does race matter? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D057.