Baseline PPIs correlate with sharply worse durvalumab outcomes in PACIFIC

Durvalumab is a PD-L1 antibody used as 12-month consolidation after concurrent chemoradiotherapy in unresectable stage III NSCLC. In a post-hoc analysis of PACIFIC treated patients consenting to exploratory analyses (n=660; durvalumab n=449; placebo n=211), baseline PPI exposure was associated with worse durvalumab PFS (9.4 vs 17.2 months; HR 1.57; p<0.0001) and OS (33.0 vs 57.9 months; HR 1.66; p<0.0001), with significant treatment-by-PPI interactions; no similar association was seen in the placebo arm. Baseline antibiotics were associated with shorter PFS on durvalumab (9.2 vs 15.6 months; HR 1.50; p=0.016) but not OS, while the overall PACIFIC benchmark remains durvalumab’s ITT benefit after cCRT (mPFS 16.9 vs 5.6 months; mOS 47.5 vs 29.1 months).