Drug-drug interactions between palbociclib and proton pump inhibitors in early breast cancer: an exploratory analysis of PALLAS (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

IF 7.1 2区医学 Q1 ONCOLOGY ESMO Open Pub Date : 2025-01-03 DOI:10.1016/j.esmoop.2024.104096

E Agostinetto, G Pfeiler, D Hlauschek, E L Mayer, M Lambertini, E de Azambuja, M Bellet-Ezquerra, J L Meisel, G Rubovszky, N Zdenkowski, Y Novik, M Ruiz-Borrego, K A Gelmon, E P Mamounas, H Iwata, D R Lu, L Soelkner, C Fesl, M Gnant, A DeMichele

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Abstract

Background: Concomitant intake of proton pump inhibitors (PPIs) may create drug-drug interactions, potentially impacting efficacy of anticancer agents. In the phase III PALLAS trial, the addition of palbociclib capsules to standard adjuvant endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer did not improve invasive disease-free survival (iDFS). We explored whether concomitant use of PPIs affected survival outcomes in patients treated with palbociclib in PALLAS.

Methods: This is an exploratory analysis of PALLAS including patients who received at least one dose of palbociclib capsules. We aimed to determine the association of concomitant PPI use with iDFS, distant relapse-free survival and overall survival. Uni- and multivariable Cox models with time-dependent PPI were used. The association between PPI use and neutropenia was also investigated.

Results: Of 2840 patients treated with palbociclib + endocrine therapy, 525 (18.5%) had concomitant PPI and palbociclib intake. PPI intake was significantly associated with older age, post-menopausal status, use of aromatase inhibitors, higher body mass index, and worse Eastern Cooperative Oncology Group status (all P < 0.001). Concomitant PPI intake was not significantly associated with survival outcomes (iDFS, distant relapse-free survival, overall survival). All-grade neutropenia rates were numerically lower in patients who initiated a PPI before study start compared with patients never initiating PPIs (adjusted odds ratio 0.81, 95% confidence interval 0.60-1.09).

Conclusions: Our exploratory analysis did not demonstrate worse survival outcomes in patients receiving concomitant palbociclib and PPIs in PALLAS. Nonetheless, careful consideration of possible drug-drug interactions is important, especially when studying novel agents in the early breast cancer setting.

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palbociclib和质子泵抑制剂在早期乳腺癌中的药物-药物相互作用：PALLAS （ABCSG-42/AFT-05/BIG-14-13/PrE0109）的探索性分析。

背景：同时摄入质子泵抑制剂（PPIs）可能会产生药物相互作用，潜在地影响抗癌药物的疗效。在III期PALLAS试验中，在激素受体阳性、人表皮生长因子受体2阴性的早期乳腺癌患者的标准辅助内分泌治疗中添加palbociclib胶囊并没有提高侵袭性无病生存期（iDFS）。我们探讨了同时使用PPIs是否会影响帕博西尼治疗的PALLAS患者的生存结果。方法：这是一项探索性分析，包括接受至少一剂帕博西尼胶囊的患者。我们的目的是确定伴随PPI使用与iDFS、远端无复发生存期和总生存期的关系。采用随时间变化的单变量和多变量Cox模型。使用PPI与中性粒细胞减少症之间的关系也被调查。结果：在2840例帕博西尼+内分泌治疗的患者中，525例（18.5%）患者同时服用PPI和帕博西尼。PPI摄入量与年龄较大、绝经后状态、芳香酶抑制剂的使用、较高的体重指数和较差的东部肿瘤合作组状态显著相关（均P < 0.001）。同时服用PPI与生存结果（iDFS、远期无复发生存、总生存）无显著相关性。在研究开始前开始使用PPI的患者与从未使用PPI的患者相比，所有级别的中性粒细胞减少率都较低（校正优势比0.81,95%可信区间0.60-1.09）。结论：我们的探索性分析并没有证明palbociclib和PPIs联合治疗的PALLAS患者的生存结果更差。尽管如此，仔细考虑可能的药物-药物相互作用是很重要的，特别是在研究早期乳腺癌的新药物时。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.