| Title: |
Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer. |
| Authors: |
Di Cosimo, S; Pérez-García, JM; Bellet, M; Dalenc, F; Gil Gil, MJ; Ruiz-Borrego, M; Gavilá, J; Aguirre, E; Schmid, P; Marmé, F; Gligorov, J; Schneeweiss, A; Albanell, J; Zamora, P; Wheatley, D; Martínez de Dueñas, E; Amillano, K; Shimizu, E; Sampayo-Cordero, M; Cortés, J; Llombart-Cussac, A |
| Publisher Information: |
Elsevier Ltd. |
| Publication Year: |
2024 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Subject Terms: |
Absorption; Advanced breast cancer; Endocrine therapy; Palbociclib; Pharmacokinetic interaction; Proton pump inhibitors; Humans; Pyridines; Female; Piperazines; Breast Neoplasms; Middle Aged; Aged; Receptor; ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Letrozole; Adult; Receptors; Estrogen; Fulvestrant; Progression-Free Survival; Progesterone; 80 and over |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Breast; https://qmro.qmul.ac.uk/xmlui/handle/123456789/101257 |
| DOI: |
10.1016/j.breast.2024.103761 |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/101257; https://doi.org/10.1016/j.breast.2024.103761 |
| Rights: |
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/). ; © 2024 The Authors. Published by Elsevier Ltd. |
| Accession Number: |
edsbas.2170BB99 |
| Database: |
BASE |