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

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. - Meth...

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Main Authors: Di Cosimo, Serena (Author) , Pérez-García, José Manuel (Author) , Bellet, Meritxell (Author) , Dalenc, Florence (Author) , Gil Gil, Miguel J. (Author) , Ruiz-Borrego, Manuel (Author) , Gavilá, Joaquín (Author) , Aguirre, Elena (Author) , Schmid, Peter (Author) , Marmé, Frederik (Author) , Gligorov, Joseph (Author) , Schneeweiss, Andreas (Author) , Albanell, Joan (Author) , Zamora, Pilar (Author) , Wheatley, Duncan (Author) , Martínez de Dueñas, Eduardo (Author) , Amillano, Kepa (Author) , Shimizu, Eileen (Author) , Sampayo-Cordero, Miguel (Author) , Cortés, Javier (Author) , Llombart-Cussac, Antonio (Author)
Format: Article (Journal)
Language:English
Published: August 2024
In: The breast
Year: 2024, Volume: 76, Pages: 1-10
ISSN:1532-3080
DOI:10.1016/j.breast.2024.103761
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.breast.2024.103761
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0960977624000924
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Author Notes:Serena Di Cosimo, José Manuel Pérez-García, Meritxell Bellet, Florence Dalenc, Miguel J. Gil Gil, Manuel Ruiz-Borrego, Joaquín Gavilá, Elena Aguirre, Peter Schmid, Frederik Marmé, Joseph Gligorov, Andreas Schneeweiss, Joan Albanell, Pilar Zamora, Duncan Wheatley, Eduardo Martínez de Dueñas, Kepa Amillano, Eileen Shimizu, Miguel Sampayo-Cordero, Javier Cortés, Antonio Llombart-Cussac
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Summary: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.
Item Description:Gesehen am 17.02.2025
Online verfügbar: 11. Juni 2024, Artikelversion: 15. Juni 2024
Physical Description:Online Resource
ISSN:1532-3080
DOI:10.1016/j.breast.2024.103761

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