Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are usually combined with fulvestrant or aromatase inhibitors for the treatment of patients with metastatic breast cancer (mBC). Drug-drug interactions may affect absorption by different mechanims, for instance, modification of digestive pH. Proton pump inhibitors (PPIs) are known to reduce the oral bioavailability of some anticancer drugs. Palbociclib is a weak base with pH-dependent solubility, therefore variations in gastric pH could affect its absorption. The objective of this study was to evaluate the interaction between PPIs and palbociclib by analizing progression-free survival (PFS) in patients with mBC.
This is a retrospective study approved by the local Ethics Committee. Patients had received palbociclib between January 2016 and December 2021. The following variables were collected: age, menopausal status, performance status, hormonal treatment (fulvestrant or aromatase inhibitors), visceral or non-visceral disease, first-line vs second-line treatment, ki67, and concomitant use of PPIs. PFS was defined as the time from starting treatment to progression of the disease. Survival was estimated with the Kaplan-Meier method, whereas Cox Regression models were used to estimate hazard ratios and the chi-square test for categorical variables.
A total of 169 patients were enrolled in the study: 80 received a PPI and 86 did not, without significant differences in clinical characteristics in both groups. The median PFS was 17.3 months (95% CI: 13.83-20.76), 36 months in first-line and 13 months in second and subsequent lines. Patients taking PPIs had a shorter median PFS (14.30 versus 42.6 months, p<0.001; HR 4.18: 95% CI 2.57-6.80; p<0.0001). Median PFS was 44 vs. 14 months in first-line ans 17 vs 9 months in second or subsequent lines. The line of treatment (first vs second or beyond) and ki67 had a significant influence on DFS, whereas the remaining clinical variables did not.
Patients with mBC treated with hormonal therapy plus palbociclib had poor PFS when receving a concomitant PPI. Although further studies are needed in the field, caution is recommended with the long-term use of PPIs in this population.
The authors.
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J. Álvarez Criado: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly. All other authors have declared no conflicts of interest.