Agostinetto E, Pfeiler G, Hlauschek D, Mayer E L, Lambertini M, de Azambuja E, Bellet-Ezquerra M, Meisel J L, Rubovszky G, Zdenkowski N, Novik Y, Ruiz-Borrego M, Gelmon K A, Mamounas E P, Iwata H, Lu D R, Soelkner L, Fesl C, Gnant M, DeMichele A
Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B.), Hôpital Universitaire de Bruxelles (H.U.B.), Brussels, Belgium.
Department of Gynecology and Gynecological Oncology, Medical University of Vienna, Vienna, Austria.
ESMO Open. 2025 Jan;10(1):104096. doi: 10.1016/j.esmoop.2024.104096. Epub 2025 Jan 3.
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.
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.
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).
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.
质子泵抑制剂（PPI）的联合使用可能会产生药物相互作用，这可能会影响抗癌药物的疗效。在III期PALLAS试验中，对于激素受体阳性、人表皮生长因子受体2阴性的早期乳腺癌患者，在标准辅助内分泌治疗中添加帕博西尼胶囊并未改善无侵袭性疾病生存期（iDFS）。我们探讨了PPI的联合使用是否会影响PALLAS试验中接受帕博西尼治疗患者的生存结局。
这是一项对PALLAS试验的探索性分析，纳入了至少接受过一剂帕博西尼胶囊治疗的患者。我们旨在确定PPI联合使用与iDFS、远处无复发生存期和总生存期之间的关联。使用了带有时间依赖性PPI的单变量和多变量Cox模型。还研究了PPI使用与中性粒细胞减少之间的关联。
在接受帕博西尼+内分泌治疗的2840例患者中，525例（18.5%）同时服用了PPI和帕博西尼。PPI的服用与年龄较大、绝经后状态、芳香化酶抑制剂的使用、较高的体重指数以及较差的东部肿瘤协作组状态显著相关（所有P<0.001）。PPI的联合服用与生存结局（iDFS、远处无复发生存期、总生存期）无显著关联。与从未开始服用PPI的患者相比，在研究开始前开始服用PPI的患者中，所有级别的中性粒细胞减少率在数值上较低（调整后的优势比为0.81，95%置信区间为0.60-1.09）。
我们的探索性分析未显示PALLAS试验中同时接受帕博西尼和PPI的患者生存结局更差。尽管如此，仔细考虑可能的药物相互作用很重要，尤其是在早期乳腺癌背景下研究新型药物时。
