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

Importance: This study highlights the potential negative 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.

Objective: To determine whether the co-administration of proton pump inhibitors (PPI) affects treatment outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with HR+ metastatic and recurrent breast cancer receiving CDK4/6i treatment.

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 (hazard ratio [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 with those without antacid 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 and relevance: The use of PPIs and H2 blockers, in combination with CDK4/6i, was 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 PPIs to patients undergoing CDK4/6i therapy.

Key points: In this retrospective analysis of 359 patients, the co-administration of PPIs with CDK4/6i was associated with significantly shorter PFS and OS. Clinicians should be cautious when prescribing PPIs to patients receiving CDK4/6i therapy due to the potential for adverse effects on treatment outcomes.