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PPIs May Curb Benefits of Palbociclib in Breast Cancer


Taking a proton pump inhibitor (PPI) with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib could diminish the full therapeutic benefit of palbociclib in women with breast cancer and lead to worse progression-free survival (PFS) and overall survival, new data suggest.


  • The study retrospectively identified 1310 women with advanced breast cancer receiving palbociclib using South Korean nationwide claims data.

  • Overall, 344 women in the concomitant group, those who were co-administered a PPI for more than one third of their palbociclib treatment duration, were propensity-score matched to 966 women who did not have PPI exposure: the nonconcomitant group.

  • Main outcomes were time to progression and death, presented as PFS and overall survival.


  • Median clinical PFS was significantly shorter by about 15 months in the concomitant PPI group vs the nonconcomitant group (25.3 vs 39.8 months; adjusted hazard ratio [HR], 1.76).

  • Concomitant PPI use was also associated with shorter overall survival (HR, 2.71).

  • Overall, 83.1% of patients in the concomitant group were alive at 1 year vs 94.0% in the nonconcomitant group (P < .001), and 69.5% vs 89.3%, respectively, were alive at 2 years (P < .001), though the median overall survival was not reached in either group.

  • In a subgroup analysis, concomitant PPI use was associated with shorter clinical PFS (HR, 1.75 for those receiving endocrine-sensitive treatment and 1.82 for those receiving endocrine-resistant treatment), and shorter overall survival (HR, 2.68 in the endocrine-sensitive subgroup and 2.98 in the endocrine-resistant subgroup).


“The findings suggest that taking PPIs with palbociclib may interrupt the full therapeutic benefits of palbociclib,” the authors conclude. “Physicians should be cautious when prescribing PPIs to patients who are receiving palbociclib.”


The study, led by Ju-Eun Lee, MS, PharmD, School of Pharmacy, Sungkyunkwan University, South Korea, was published online July 21 in JAMA Network Open.


The study was limited by its retrospective design and use of claims data as well as the inability to confirm whether patients actually took the PPI medication.


The authors report no relevant financial relationships. The study reported no commercial funding.

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  • Posted on August 7, 2023