The results of a study showed that the median progression-free survival was shorter for patients with advanced breast cancer who use proton pump inhibitors with palbociclib.
The use of proton pump inhibitors (PPI) could negatively affect the therapeutic benefits of palbociclib in patients with breast cancer, according to the results of a study published in JAMA Network Open. PPIs are commonly used to help relieve gastrointestinal symptoms; however, they can also negatively affect the clinical outcomes of oral concomitant drugs, according to the study authors.
Investigators aimed to identify whether clinical outcomes are affected for individuals with advanced breast cancer who use PPIs in addition to treatment with palbociclib. Data were collected between November 1, 2016, and July 31, 2021, in South Korea. Individuals with breast cancer who were receiving palbociclib were identified between November 1, 2017, and July 31, 2020. Investigators classified individuals into the concomitant PPI group if there was at least a 33% overlap of palbociclib and PPIs. Those who never received PPI during their treatment period were classified into the non-concomitant PPI cohort.
The main outcomes of the study were time to progression and death, which were presented as progression-free survival (PFS) and overall survival (OS). Investigators used the Kaplan-Meier method and log-rank test as well as a Cox proportional hazards regression to estimate the hazard ratio (HR) of the concomitant use associated with PFS and OS.
Investigators included a total of 344 women in the concomitant PPI group and 966 in the non-concomitant PPI group. Individuals were matched 1:3 for the analysis. Approximately 84.6% were older than 50 years of age, 84.8% were treated with letrozole and anastrozole, and 15.2% were treated with fulvestrant. The majority of individuals did not receive chemotherapy or endocrine therapy prior to palbociclib.
Results of the study showed that the median clinical PFS in the PPI group was shorter than those in the non-concomitant PPI group at 25.3 and 39.8 months, respectively; with an HR of 1.76.
Additionally, the study authors reported that the concomitant use was also associated with shorter OS, with an HR of 2.71. The 1-year OS was 83.1% for those in the concomitant PPI group and 94% for those in the non-concomitant PPI group. The 2-year OS was 69.5% and 89.3%, respectively; however, the median OS in both groups were not reached, according to the study.
Both clinical PFS and OS in the concomitant PPI group were consistently poor in those who were receiving endocrine-sensitive and endocrine-resistant treatment. The median clinical PFS for the non-concomitant PPI group who received endocrine-sensitive treatment was 40.4 months compared to the concomitant group at 27.2 months.
When investigators increased the coverage ratios of the concomitant group to 50%, 67%, and 80%, there was an increased risk associated with PFS and OS. The same trend was also observed in cohorts that were constructed at the 3-, 6-, and 12-month periods.
The study authors cautioned physicians who prescribe PPIs to patients treated with palbociclib, saying that they should be advised about the risks of interaction to prevent risks for adverse outcomes.
Lee J, Kwon S, Kwon S, Jung H, Nam JH, Lee E. Concomitant use of proton pump inhibitors and palbociclib among patients with breast cancer. JAMA Netw Open. 2023;6(7):e2324852. doi:10.1001/jamanetworkopen.2023.24852