OBJECTIVES: Palbociclib is a weak base medication whose absorption may be inhibited by a concomitant proton pump inhibitor (PPI). We aimed to identify the clinical impact of concomitant use of PPI and palbociclib in patients with advanced breast cancer using nationwide claims data in South Korea.

METHODS: We identified patients with breast cancer taking palbociclib between Nov 2017, and Jul 2020, using claims data from the Health Insurance Review & Assessment Service (HIRA). Patients whose prescriptions for palbociclib and PPI overlapped by more than 30% were classified as PPI group and patients who had never taken PPI during the palbociclib period were classified as non-PPI group. They were matched using propensity score (PS). We used the Kaplan-Meier method and log-rank test to compare time to next treatment (TTNT), defined as the period until the start of subsequent therapy or death, between two groups. Hazard ratio (HR) was estimated using a cox proportional hazard model with covariates including age, menopause, metastasis, comorbidity, prior therapy, and concomitant drugs.

RESULTS: Among 3,339 patients with breast cancer taking palbociclib, 344 patients were assigned to PPI and 1587 to non-PPI group after matching. In PPI group, 291 patients (84.6%) were treated with a non-steroidal aromatase inhibitor (NSAI) and 53 patients (15.4%) were treated with fulvestrant. The median TTNT was 25.3 months in PPI group and 39.8 months in non-PPI group (P-value <0.001). The risk for TTNT was significantly higher in the PPI group compared to non-PPI group (all aHR: 1.74, 1.46 – 2.08; NSAI aHR: 1.73, 1.42 – 2.10; fulvestrant aHR: 1.83, 1.17 - 2.87). Concomitant PPI was the independent factor associated with risk for TTNT (P<0.0001).

CONCLUSIONS: This real-world analysis found that concomitant use of PPI and palbociclib increase the risk for TTNT compared to the palbociclib alone. PPI should be carefully prescribed in patients taking palbociclib.