The human microbiome can play an important, thought not fully understood, role in immune modulation and response to immunotherapy. This post hoc analysis of PACFIC sought to determine if baseline exposure to antibiotics or proton pump inhibitors influenced the response to durvalumab following chemoradiation for locally advanced NSCLC. The study included 660 PACIFIC patients, of whom 40% had baseline PPI exposure and 10% had baseline antibiotic exposure. Among those who received durvalumab, baseline PPI exposure was associated with significantly shorter PFS (9.4 v 17.2 months) and OS (33 v 57.9 months). Likewise, baseline antibiotic exposure was also associated with lower PFS (9.2 v 15.6 months), but not OS. Among those who received placebo, there was no association between antibiotic or PPI exposure and survival outcomes. This suggests gut microbiome modulation with antibiotics or PPI may attenuate immunotherapy response. | Brunetti, Lancet Oncol 2026
