Proton Pump Inhibitor and Antibiotic Use May Reduce the Benefit of Immunotherapy in NSCLC

Baseline use of proton pump inhibitors (PPIs) and, to a lesser extent, antibiotics was associated with poorer outcomes in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with durvalumab after chemoradiotherapy, suggesting these medications may reduce the benefit of immunotherapy. This post-hoc analysis of the phase 3 PACIFIC trial included 660 patients with unresectable stage III NSCLC who had not progressed after concurrent chemoradiotherapy and received either durvalumab or placebo. Forty percent of patients had baseline PPI exposure and 10% had baseline antibiotic exposure. Among patients treated with durvalumab, baseline PPI use was associated with significantly shorter progression-free survival (9.4 vs 17.2 months; HR 1.57) and overall survival (33.0 vs 57.9 months; HR 1.66) compared with no PPI exposure. Baseline antibiotic use was also associated with shorter progression-free survival (9.2 vs 15.6 months; HR 1.50), although its association with overall survival was not statistically significant. In contrast, neither PPIs nor antibiotics affected progression-free or overall survival in the placebo group. These findings support the hypothesis that disruption of the gut microbiome by PPIs or antibiotics may attenuate the efficacy of durvalumab in patients with unresectable stage III NSCLC. Source: https://www.thelancet.com/