Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer

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• dc.contributor.author Di Cosimo, Serena
• dc.contributor.author Albanell Mestres, Joan
• dc.contributor.author Llombart-Cussac, Antonio
• dc.date.accessioned 2025-03-07T07:06:09Z
• dc.date.available 2025-03-07T07:06:09Z
• dc.date.issued 2024
• dc.description.abstract Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. Methods: First-line endocrine-sensitive, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-naïve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least ≥⅔ of treatment, respectively. PPI groups were not mutually exclusive. Results: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1-2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0-1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade ≥3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). Conclusions: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR+/HER2- ABC.
• dc.format.mimetype application/pdf
• dc.identifier.citation Di Cosimo S, Pérez-García JM, Bellet M, Dalenc F, Gil Gil MJ, Ruiz-Borrego M, et al. Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer. Breast. 2024 Aug;76:103761. DOI: 10.1016/j.breast.2024.103761
• dc.identifier.doi http://dx.doi.org/10.1016/j.breast.2024.103761
• dc.identifier.issn 0960-9776
• dc.identifier.uri http://hdl.handle.net/10230/69847
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Breast. 2024 Aug;76:103761
• dc.rights © 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Absorption
• dc.subject.keyword Advanced breast cancer
• dc.subject.keyword Endocrine therapy
• dc.subject.keyword Palbociclib
• dc.subject.keyword Pharmacokinetic interaction
• dc.subject.keyword Proton pump inhibitors
• dc.title Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion