Proton Pump Inhibitors and Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Breast Cancer

• Published in: The oncologist (Dayton, Ohio) Ohio), 2024-06, Vol.29 (6), p.e741-e749
• Main Authors: Takahashi, Kaori, Uozumi, Ryuji, Mukohara, Toru, Hayashida, Tetsu, Iwabe, Midori, Iihara, Hirotoshi, Kusuhara-Mamishin, Kanako, Kitagawa, Yuko, Tsuchiya, Masami, Kitahora, Mika, Nagayama, Aiko, Kosaka, Shinkichi, Asano-Niwa, Yoshimi, Seki, Tomoko, Ohnuki, Koji, Suzuki, Akio, Ono, Fumiko, Futamura, Manabu, Kawazoe, Hitoshi, Nakamura, Tomonori
• Format: Article
• Language: English
• Subjects: Analysis; Breast Cancer; Complications and side effects; Dosage and administration; Drug interactions; Drug therapy; Drug therapy, Combination; Proton pump inhibitors
• ISSN: 1083-7159; 1549-490X; 1549-490X
• DOI: 10.1093/oncolo/oyae015

Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment. This multicenter, retrospective, observational study, conducted across 4 medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022. Propensity score-matched analyses were performed. Treatment efficacy and safety with and without PPIs were compared. Progression-free survival and overall survival were estimated using the Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio. The study included 240 patients. After 1:1 matching, 112 patients were treated with and without PPIs. The median progression-free survival period was 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% CI, 0.70-2.02). The median overall survival period was 3.6 years in the PPI group, whereas it was not reached in the non-PPI group (hazard ratio, 1.23; 95% CI, 0.61-2.47). Consistent results were obtained for subgroups receiving palbociclib (n = 177) and abemaciclib (n = 63) without propensity score matching. Adverse event incidence and severity were similar in both groups. The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted.