Seoul, South Korea—The use of PPIs by cancer patients is common as they try to mitigate anticancer drug–related gastrointestinal symptoms, such as gastroesophageal reflux disease. A new study cautioned, however, that use of PPIs can tamp down the effect of some oral cancer medications, specifically in breast cancer.

The report in the Journal of the American Medical Association Network Open pointed out that PPIs irreversibly bind to and inhibit the hydrogen-potassium adenosine triphosphatase pump located on the luminal surface of the parietal cell membrane, reducing the secretion of gastric acid. “However, acid suppression negatively affects the oral bioavailability, pharmacokinetics, and clinical effects of orally administered anticancer medications,” wrote the South Korean researchers. “For this reason, PPIs could be considered to have a high risk of drug-drug interaction with other anticancer drugs.”

To identify the clinical outcomes of patients with advanced breast cancer who concomitantly use PPIs and palbociclib, the study team performed a retrospective cohort study using nationwide claims data between November 1, 2016, and July 31, 2021, in South Korea.

The study identified patients with breast cancer receiving palbociclib, and the 334 women whose prescriptions for palbociclib and PPI overlapped by at least 33% were classified into a concomitant PPI group. At the same time, 966 patients who never received a PPI during the palbociclib treatment period were classified into a nonconcomitant PPI group.

The focus was on the time to progression and death, presented as progression-free survival (PFS) and overall survival (OS). Most patients (84.6%) were aged older than 50 years, with 84.8% treated with letrozole and anastrozole (endocrine sensitive) and 15.2% treated with fulvestrant (endocrine resistant).

The results indicated that the median clinical PFS in the concomitant PPI group was shorter than that of the nonconcomitant PPI group (25.3 [95% CI, 19.6-33.0] vs. 39.8 [95% CI, 34.9] to not applicable] months; P <.001), and the hazard ratio (HR) was 1.76 (95% CI, 1.46-2.13).

“Concomitant use of PPI was also associated with shorter OS (HR 2.71 [95% CI, 2.07-3.53]),” the authors wrote. “Both clinical PFS and OS in the concomitant PPI group were consistently poor in patients receiving endocrine-sensitive and endocrine-resistant treatment.”

The study concluded that concomitant use of PPIs with palbociclib “may hinder the complete therapeutic benefits of palbociclib in patients with breast cancer.”

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