Association between concomitant proton pump inhibitor use and survival of patients with metastatic prostate cancer receiving abiraterone acetate: a post-hoc analysis of pooled data from three randomized controlled trials

Wataru Fukuokaya; Keiichiro Mori; Takafumi Yanagisawa; Kohei Akazawa; Tatsuya Shimomura; Takahiro Kimura

doi:10.1038/s41391-023-00695-x

Association between concomitant proton pump inhibitor use and survival of patients with metastatic prostate cancer receiving abiraterone acetate: a post-hoc analysis of pooled data from three randomized controlled trials

Prostate Cancer Prostatic Dis. 2023 Jul 18. doi: 10.1038/s41391-023-00695-x. Online ahead of print.

Authors

Wataru Fukuokaya¹, Keiichiro Mori², Takafumi Yanagisawa², Kohei Akazawa³, Tatsuya Shimomura², Takahiro Kimura²

Affiliations

¹ Department of Urology, The Jikei University School of Medicine; 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan. wfukuokaya@gmail.com.
² Department of Urology, The Jikei University School of Medicine; 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
³ Department of Medical Informatics, Niigata University Medical and Dental Hospital; 1-754 Asahimachi-dori, Chuo-ku, Niigata, Japan.

PMID: 37464102
DOI: 10.1038/s41391-023-00695-x

Abstract

Background: Evidence suggests proton pump inhibitor (PPI) use may attenuate the effect of abiraterone acetate plus prednisone (AAP) in metastatic prostate cancer via the modification of gut microbiota. This study aimed to examine whether concomitant PPI use is associated with survival in patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT) and AAP.

Methods: Post-hoc analysis was conducted in patients with metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC) treated in the LATITUDE, COU-AA-301, and COU-AA-302 trials (ADT vs. ADT plus AAP). PPI users and non-users were compared for restricted mean overall survival time (RMOST) and restricted mean progression-free survival time (RMPFST) based on inverse probability of treatment weight (IPTW)-adjusted Kaplan-Meier curves. IPTW-adjusted Cox regression models were used to assess heterogeneity of treatment effect.

Results: In patients treated with AAP, PPI use was associated with inferior RMOST [difference (95% confidence interval): -4.2 (-7.0 to -1.4)] and RMPFST [-3.5 (-6.6 to -0.4)] compared with non-users. However, RMOST and RMPFST were similar between PPI users and non-users in patients treated with ADT alone [RMOST, -2.6 (-5.8 to 0.6); RMPFST, -1.7 (-4.8 to 1.4)]. Interaction term analyses did not show evidence of heterogeneity in treatment effect between AAP and ADT, despite the prominent treatment effect shown in mCSPC vs. mCRPC.

Conclusions: PPI use may be associated with inferior survival in patients with metastatic prostate cancer who receive ADT plus AAP. Discontinuing unnecessary PPI use might improve those outcomes.