Drug-drug interactions between palbociclib and proton pump inhibitors in early breast cancer: an exploratory analysis of PALLAS (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.