TITLE:
Impact of Drug-Drug Interaction between CDK4/6 Inhibitors and Proton Pump Inhibitors on Survival Outcomes in the Treatment of Metastatic Breast Cancer—Real World Data from a Portuguese Center
AUTHORS:
Joana Reis, Inês Costa, Mariana Costa, Ana Valente, Catarina Almeida, Marta Freitas, Cláudia Caeiro, Catarina Fernandes, Nuno Tavares, Miguel Barbosa
KEYWORDS:
Drug Interaction, Survival Impact, Advanced Breast Cancer, CDK4/6 Inhibitors, Proton Pump Inhibitors
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.13 No.5,
May
30,
2022
ABSTRACT: Introduction: Proton pump inhibitors (PPi) are widely prescribed,
including in patients undergoing treatment for advanced breast cancer (ABC).
Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a
drug interaction with PPi was hypothesized. It was shown in a retrospective
study that this association was an independent predictive factor for worse
progression-free survival (PFS). Objective: To verify the impact of concomitant
administration of PPi with Ci on
overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for
HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for
data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and
multivariate analysis by COX regression. P-value - 75).
Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib
in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and
fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant
PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS
med 15 m. vs. 21 m., p = 0.733), although with no statistically significant
difference. Discussion: In the sample, there
was a numerical difference, without the statistical significance in the use
of PPi in the survival of patients under Ci. This difference could be more
evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for
drug interactions. Polymedication, advanced age and the presence of several
comorbidities are real problems in patients with ABC. Conclusion: Real-world
data from this center demonstrate a negative, non-statistically significant
impact of PPi treatment on survival outcomes, in patients treated with Ci for
HR+HER2-ABC.