Association between antibiotic use and mortality among older persons receiving first-line immune checkpoint inhibitors for non-small cell lung cancer (NSCLC).
Authors: Chaya Goldberg, Julia Nelson, Melanie Rua, Rajat Bannerji, Soko Setoguchi, Benjamin Bates
Journal: Journal of Clinical Oncology (2024)

e14607 Background: There is biologic plausibility that antibiotics (ABX) may reduce the effectiveness of cancer therapy, most notably immune checkpoint inhibitors (ICI). As ABX are commonly prescribed to older persons and more than a third of US persons with cancer are eligible for ICIs, use of ABX has important population health implications. We assess the association between ABX use and mortality among persons with NSCLC who receive first-line (1L) treatment. Methods: Using SEER-Medicare, we assembled a cohort of persons ≥66 years with NSCLC who received 1L treatment with platinum-based chemotherapy (PLT) or ICI (PLT without ICI, PLT with ICI, and ICI monotherapy) within one year of cancer diagnosis between 2017-2019. We assessed overall ABX exposure from 1 month to 1 year prior to treatment initiation and by ABX class. Primary outcome was all cause deaths within three years of treatment initiation or until 12/31/2020. Multivariable Cox proportional hazard models adjusting for individual-level characteristics (demographics, time-to-treatment, comorbidities, healthcare use, SEER registry, and neighborhood socioeconomic status) and landmark analyses of 1-6 months after cancer treatment were used to assess the association between ABX exposure and mortality. Results: Among 4,182 persons (mean age 75 years, 85% white, 68% chemo-immunotherapy within 2 months of NSCLC diagnosis), 63%, 18%, and 18% received PLT, PLT+ICI, and ICI, respectively. ICI+/-PLT increased in prevalence from 20% of treatments (2017) to 55% (2019). The mean age of persons who received ICI alone (78 years old) was higher than PLT or PLT+ICI. Prior to 1L treatment, 22% and 72% of persons received ABX within 30 days and 1 year prior to cancer treatment, respectively. The three most common ABX classes were fluoroquinolones (48%), penicillins (21%), and macrolides (18%). The cohort was followed for 3,274 person-years and included 2,958 deaths within 1 year and 4,144 deaths within 3 years of follow-up. Compared with persons who did not receive ABX within 3 months of cancer treatment, ABX use was associated with higher risk of death within 3 years for ICI alone [HR 1.24 (1.05-1.46) but not for PLT alone or PLT+ICI. Fluoroquinolones were associated with an elevated risk of mortality among persons who received ICI alone HR 1.41(95%CI: 1.1-1.8) and PLT alone HR 1.18 (95%CI: 1.05-1.32) but not PLT+ICI. Our findings were similar across definitions of ABX exposure (30 days to 1 year prior to treatment) and analytic landmarks after treatment initiation. Conclusions: Among patients with NSCLC who received 1L treatment, we identified an association between ABX exposure prior to treatment and increased mortality among persons who received ICI monotherapy but not PLT+ICI. As ICIs expand to more cancer types and earlier stages, ABX use may have a significant impact on outcomes and population health.