Proton pump inhibitors (PPIs) diminish the absorption levels of multiple oncology agents. The potential influence of PPIs when administered alongside cyclin-dependent kinase 4/6 inhibitors remains under debate. This investigation sought to establish if concurrent PPI administration alters the therapeutic benefits of palbociclib and abemaciclib in managing breast cancer. A retrospective observational analysis was performed across multiple centers involving 4 healthcare facilities in Japan. Eligible participants were sequentially recruited individuals diagnosed with hormone therapy-resistant advanced breast cancer who initiated treatment with either palbociclib or abemaciclib from December 2017 through August 2022. Matching based on propensity scores was implemented. Clinical outcomes and tolerability profiles were evaluated between cohorts with and without PPI exposure. Kaplan-Meier estimates were generated for progression-free and overall survival, with differences assessed via log-rank testing. Hazard ratios were derived from Cox regression modeling. Overall, 240 cases were analyzed. Following 1:1 propensity matching, 112 subjects remained in each arm. The median duration of progression-free survival stood at 1.2 years among PPI recipients versus 1.3 years in those avoiding PPIs (hazard ratio, 1.19; 95% CI, 0.70-2.02). Overall survival reached a median of 3.6 years in the PPI arm, while it remained undetermined in the comparator arm (hazard ratio, 1.23; 95% CI, 0.61-2.47). Comparable patterns emerged in unmapped cohorts treated with palbociclib (n = 177) or abemaciclib (n = 63). Toxicity profiles, including frequency and intensity, showed no notable differences across arms. Concurrent administration of PPIs does not appear to compromise the clinical performance of cyclin-dependent kinase 4/6 inhibitors. Additional forward-looking investigations focused on pharmacokinetics are advised.
