Effect of Proton-Pump Inhibitor on Survival in Chinese Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer Receiving Upfront Combinatorial Docetaxel Treatment

Objective: There is a growing indication of the effect of proton-pump inhibitors (PPI). Drug–drug interaction between PPI and anti-tumoral treatment has been postulated. Existing analyses from trial data have shown that PPI usage was associated with inferior survival in metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and androgen deprivation therapy (ADT). The interaction between PPI and chemotherapy remains, however, unexplored. We seek to investigate the impact of PPI usage in mHSPC patients treated with upfront docetaxel and ADT. Patients and Methods: A prospectively maintained database was retrieved. Patients diagnosed with de novo mHSPC from 2016 to 2022 treated with upfront docetaxel (defined as being delivered within 6 months of ADT initiation) were included. The cohort was classified into those on PPI versus those who were not. A landmark analysis was performed at 6 months from treatment initiation. Outcomes included overall survival (OS), CRPC-free survival, and PSA kinetics. Multivariate Cox regression analysis was performed on survival outcomes. Results: One hundred and one patients were included in the study, with 79 patients in the No-PPI group and 22 in the PPI group. The median follow-up duration was 39.3 and 29.6 months, respectively. The proportion of patients that reached a PSA nadir of <0.1 ng/dL was higher in the non-PPI group (19.0% vs. 4.5%, p = 0.041). PPI usage was associated with inferior OS (OR = 2.28; 95%CI = 1.112–4.675; p = 0.025). In multivariate regression analysis, PPI usage was the only statistically significant factor for OS (p = 0.036). Conclusions: PPI usage was associated with inferior oncological outcomes in de novo mHSPC patients treated with upfront docetaxel. Its judicious use is advised.