Real-world evaluation of CDK4/6 inhibitors in hormone receptor-positive metastatic breast cancer: Prognostic effect of proton pump inhibitor use

Background This study evaluates the prognostic impact of the co-administration of proton pump inhibitors (PPI) on treatment outcomes in patients with hormone receptor-positive (HR+) metastatic and recurrent breast cancer who were receiving CDK4/6 inhibitor(CDK4/6i) treatment, providing real-world evidence to guide treatment strategies. Materials and Methods This retrospective analysis included 359 patients with HR+ metastasis and relapse breast cancer treated between 2018 and 2023. Patient characteristics and outcomes were compared between those receiving CDK4/6i plus endocrine therapy without any antacid medications and those with a combination of either PPI or H2 receptor blockers. Results There were 55.7% patients in the no-antacid group, 33.1% in the PPI group, and 11.1% in the H2-blocker only group. Patients receiving PPI in combination with CDK4/6i and endocrine therapy had significantly shorter PFS(HR = 2.298, p < 0.001) and OS(HR = 3.03, p < 0.001). The H2 blocker group also showed a trend toward poorer PFS(HR = 1.987, p < 0.001) and OS compared to those without antiacid use (HR = 3.380, p = 0.226). These trends were shown in both the overall cohort and first-line treatment, regardless of the specific CDK4/6i used. No significant differences were observed between types of PPIs. Additionally, increased PPI usage time proportion during CDK4/6i treatment was associated with a higher risk of disease progression and mortality. Conclusion The use of PPIs and H2 blockers, in combination with CDK4/6i is associated with adverse effects on PFS and OS in patients with HR+ metastatic or recurrent breast cancer in a real-world setting. Clinicians should exercise caution when prescribing proton pump inhibitors to patients undergoing CDK4/6 inhibitor therapy.