Concomitant intake of proton pump inhibitors (PPIs) may create drug-drug interactions,
potentially impacting efficacy of anticancer agents. In the phase III PALLAS trial,
the addition of palbociclib capsules to standard adjuvant endocrine therapy in patients
with hormone receptor-positive, human epidermal growth factor receptor 2-negative
early breast cancer did not improve invasive disease-free survival (iDFS). We explored
whether concomitant use of PPIs affected survival outcomes in patients treated with
palbociclib in PALLAS.This is an exploratory analysis of PALLAS including patients
who received at least one dose of palbociclib capsules. We aimed to determine the
association of concomitant PPI use with iDFS, distant relapse-free survival and overall
survival. Uni- and multivariable Cox models with time-dependent PPI were used. The
association between PPI use and neutropenia was also investigated.Of 2840 patients
treated with palbociclib + endocrine therapy, 525 (18.5%) had concomitant PPI and
palbociclib intake. PPI intake was significantly associated with older age, post-menopausal
status, use of aromatase inhibitors, higher body mass index, and worse Eastern Cooperative
Oncology Group status (all P < 0.001). Concomitant PPI intake was not significantly
associated with survival outcomes (iDFS, distant relapse-free survival, overall survival).
All-grade neutropenia rates were numerically lower in patients who initiated a PPI
before study start compared with patients never initiating PPIs (adjusted odds ratio
0.81, 95% confidence interval 0.60-1.09).Our exploratory analysis did not demonstrate
worse survival outcomes in patients receiving concomitant palbociclib and PPIs in
PALLAS. Nonetheless, careful consideration of possible drug-drug interactions is important,
especially when studying novel agents in the early breast cancer setting.
