Pooled analysis of nearly 23,000 patients shows medication commonly used for acid reflux may interfere with cancer treatment effectiveness.
Proton pump inhibitor use was associated with significantly poorer overall survival, progression-free survival, and increased grade 3 or higher adverse events in breast cancer patients, according to a study published in Cancer Medicine.
Among 23,211 patients pooled from 19 breast cancer clinical trials, proton pump inhibitor (PPI) use at baseline was associated with worse outcomes across multiple measures.
Researchers pooled individual participant data from 19 trials including CLEOPATRA, EMILIA, MONARCH1-3, PALOMA1-3, APHINITY, HERA, and KATHERINE. The analysis included 13,837 patients with early-stage disease and 9,374 with advanced disease. At baseline, 8% of patients were using PPIs, 12% were on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), 8% were taking beta-blockers, and 7% were using statins.
Cox proportional hazards models and logistic regression analyses assessed associations between baseline concomitant medication use and outcomes, adjusting for age, body mass index, estrogen receptor status, performance status, comorbidity count, and relevant comorbidities. The median age was 52 years, and 50% of participants were female.
Beta-blockers, ACE inhibitors or ARBs, and calcium channel blockers were associated with higher adverse event rates but showed no statistically significant impact on survival outcomes. Statins and metformin demonstrated no statistically significant associations with either survival or adverse events.
Researchers proposed that PPIs may worsen cancer outcomes through disruption of the gut microbiota-immune system axis, which plays a crucial role in regulating systemic immune responses important for anti-tumor activity. Additionally, PPIs may alter the pharmacokinetics of anticancer therapies, including CDK4/6 inhibitors, chemotherapy agents, and immune checkpoint inhibitors, potentially reducing their effectiveness.
"These findings emphasize the need for careful management of concomitant medications in breast cancer care and support ongoing research to optimize treatment safety and efficacy," wrote lead study author Natansh D. Modi, PhD, of Flinders University, College of Medicine and Public Health, Adelaide, Australia, and colleagues.
The study had several limitations. As a pooled analysis of clinical trial data, the research was observational in nature and could not establish causation. Information on PPI dosage, duration of use, and specific indications for prescription was not available. The analysis also lacked data on changes in PPI use during the treatment period, and residual confounding from unmeasured variables could not be ruled out.
Several authors reported receiving investigator-initiated funding for research outside the scope of the current study from AstraZeneca, Boehringer Ingelheim, Pfizer, and Takeda. Some authors reported receiving consulting fees from pharmaceutical companies. The funders had no role in the study design, data collection, analysis, interpretation, or decision to submit the article for publication. Full disclosures can be found in the study.
Source: Wiley Online Library
