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Observational Study
. 2024 Jun 3;29(6):e741-e749.
doi: 10.1093/oncolo/oyae015.

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

Kaori Takahashi  1 , Ryuji Uozumi  2 , Toru Mukohara  3 , Tetsu Hayashida  4 , Midori Iwabe  5 , Hirotoshi Iihara  6 , Kanako Kusuhara-Mamishin  7 , Yuko Kitagawa  4 , Masami Tsuchiya  5 , Mika Kitahora  6 , Aiko Nagayama  4 , Shinkichi Kosaka  8 , Yoshimi Asano-Niwa  9 , Tomoko Seki  4 , Koji Ohnuki  10 , Akio Suzuki  6 , Fumiko Ono  4 , Manabu Futamura  9 , Hitoshi Kawazoe  1   11 , Tomonori Nakamura  1   11
Affiliations
Observational Study

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

Kaori Takahashi et al. Oncologist. .

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusion: The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted.

Keywords: abemaciclib; breast cancer; palbociclib; propensity score; proton pump inhibitor.

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Conflict of interest statement

R.U. received personal fees from Eisai, Sawai Pharmaceutical, SBI Pharmaceuticals, Daiichi Sankyo, Statcom, and EPS Corporation, and lecture fees from Janssen Pharmaceutical and SAS Institute Japan outside the submitted work. T.M. received grants from Sysmex, Eisai, MSD, Pfizer, Novartis, Chugai, AstraZeneca, Ono, Daiichi Sankyo, and Gilead Sciences and lecture fees from Eisai, Pfizer, Novartis, Chugai, Eli Lilly, AstraZeneca, Kyowa Kirin, Taiho, and Daiichi Sankyo outside the submitted work. T.H. received a research grant from Eli Lilly and lecture fees from Eli Lilly and Pfizer outside the submitted work. H.I. received consulting fees from Taiho, consulting fees provided to the institution from Eisai and Taiho, and lecture fees from Astellas, AstraZeneca, Chugai, Daiichi Sankyo, Eli Lilly, Nippon Boehringer Ingelheim, Nippon Kayaku, Ono, Taiho, and Yakult outside the submitted work. K.K. received payment for presentations from Daiichi Sankyo and Merck Serono, and payment for expert testimony from Daiichi Sankyo outside the submitted work. Y.K. received grants provided to the institution from Asahi Kasei, Ono, Otsuka, Nippon Covidien, Taiho, Chugai, Kaken, EA Pharma, Yakult, Otsuka, Tsumura, Sumitomo, Eisai, Kyowa Kirin, Takeda, Teijin, Cardinal Health, and Kowa, and personal fees from Asahi Kasei, AstraZeneca, Ethicon, Ono, Otsuka, Olympus, Cardinal Health, Shionogi, Taiho, Chugai, Bristol-Myers Squibb, MSD, Smith & Nephew, Kaken, Aska, Miyarisan, Toray Industries, Daiichi Sankyo, Chugai Foundation for Innovative Drug Discovery Science, Nippon Kayaku, EA Pharma, Intuitive Surgical, Takeda, Sysmex, and Tsumura, and joint research laboratory for development and education of innovative medical technology of Sysmex and Medicaroid corporation outside the submitted work. M.K. received a lecture fee from Eisai outside the submitted work. A.N. received lecture fees from Chugai, Pfizer, and Daiichi Sankyo and owns stock of Chugai. A.S. received grants provided to the institution from Nippon Kayaku, Asahi Kasei, Chugai, Taiho, Daiichi Sankyo, Japan Blood Products Organization, Mochida, and Sun Pharma, and lecture fees from Toa Eiyo, Asahi Kasei, Daiichi Sankyo, Pfizer, Eisai, Nippon Shinyaku, Celltrion Healthcare Japan, Otsuka, Sandoz, Tsumura, Nipro, Taiho, Kyowa Kirin, Nippon Chemiphar, Japan Blood Products Organization, Takeda, and Nippon Boehringer Ingelheim outside the submitted work. M.F. received lecture fees from Daiichi Sankyo, Taiho, Chugai, Eisai, Eli Lilly, and Nippon Kayaku outside the submitted work. H.K. received research funding from Eli Lilly outside the submitted work. T.N. received research funding from Chugai, Daiichi Sankyo, Kyowa Kirin, Otsuka, Sanofi, and Shionogi outside the submitted work. The other authors declared no Conflict of Interest. The aforementioned funders had no role in the design, conduct, or reporting of this study.

Figures

Figure 1.
Figure 1.
Patient enrollment flowchart. Abbreviations: HER2, human epidermal growth factor receptor type 2; CDK4/6, cyclin-dependent kinases 4 and 6; PPI, proton pump inhibitor.
Figure 2.
Figure 2.
Kaplan-Meier survival curves according to concomitant or non-concomitant PPI use. Kaplan-Meier survival curves were constructed according to the use of PPIs in the propensity score-matched patients. Solid and dashed lines represent the PPI and non-PPI groups, respectively. The number of patients at risk are shown at the bottom. (A) Progression-free survival. (B) Overall survival. Abbreviation: PPI, proton pump inhibitor.
See this image and copyright information in PMC

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