帕博西尼联合内分泌治疗用于激素受体阳性/人表皮生长因子受体 2 阴性晚期乳腺癌的长期 pooled 安全性分析：最多 5 年随访的更新分析。

Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up.

机构信息

David Geffen School of Medicine at the University of California Los Angeles, Santa Monica, California, USA.

University of California San Francisco Comprehensive Cancer Center, San Francisco, California, USA.

出版信息

Oncologist. 2021 May;26(5):e749-e755. doi: 10.1002/onco.13684. Epub 2021 Mar 10.

DOI:10.1002/onco.13684

PMID:33486783

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8100571/

Abstract

BACKGROUND

Previous studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer palbociclib treatment exposure.

PATIENTS AND METHODS

Data were pooled from three randomized studies of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic treatment for advanced disease (PALOMA-1/-2) and pre- and postmenopausal women who had progressed on prior ET (PALOMA-3).

RESULTS

Updated cutoff dates were December 21, 2017 (PALOMA-1), May 31, 2017 (PALOMA-2), and April 13, 2018 (PALOMA-3). Total person-years of treatment exposure were 1,421.6 with palbociclib plus ET (n = 872) and 528.4 with ET (n = 471). Any-grade neutropenia and infections were more frequent with palbociclib plus ET (82.1% and 59.2%, respectively) than with ET (5.1% and 39.5%). The hazard ratios were 1.6 (p = .0995) for grade 3/4 infections, 1.8 (p = .4358) for grade 3/4 viral infections, 1.4 (p = .0001) for infections, and 30.8 (p < .0001) for neutropenia. Febrile neutropenia was reported in 1.4% of patients receiving palbociclib plus ET. Cumulative incidence of all-grade hematologic adverse events in both arms peaked during the first year of treatment and plateaued over the 5 subsequent years. Interstitial lung disease was reported in 13 patients receiving palbociclib plus ET and 3 receiving ET.

CONCLUSION

This 5-year, long-term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/HER2- ABC.

IMPLICATIONS FOR PRACTICE

Several treatments for patients with breast cancer are associated with long-term or latent adverse events. This long-term, 5-year analysis demonstrated that palbociclib plus endocrine therapy has a consistent and stable safety profile without cumulative or delayed toxicities. These results further support palbociclib plus endocrine therapy as a safe and manageable treatment in clinical practice for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.

摘要

背景

先前的研究表明，帕博西尼联合内分泌治疗（ET）具有良好的耐受性。本分析基于最近的截止日期和更长的帕博西尼治疗暴露时间来评估安全性。

患者和方法

本研究数据来自三项针对激素受体阳性/人表皮生长因子受体 2 阴性（HR+/HER2-）晚期乳腺癌（ABC）患者的随机研究，包括未接受过晚期疾病系统治疗的绝经后女性（PALOMA-1/-2）和接受过前期和后期 ET 治疗的绝经前和绝经后女性（PALOMA-3）。

结果

更新的截止日期为 2017 年 12 月 21 日（PALOMA-1）、2017 年 5 月 31 日（PALOMA-2）和 2018 年 4 月 13 日（PALOMA-3）。帕博西尼联合 ET 组的总治疗暴露人年数为 1421.6（n = 872），ET 组为 528.4（n = 471）。与 ET 组相比（分别为 5.1%和 39.5%），帕博西尼联合 ET 组更常见任何级别中性粒细胞减少症和感染（分别为 82.1%和 59.2%）。与 ET 组相比，3/4 级感染（风险比 [HR]，1.6；p =.0995）、3/4 级病毒感染（HR，1.8；p =.4358）、感染（HR，1.4；p =.0001）和中性粒细胞减少症（HR，30.8；p <.0001）的风险更高。接受帕博西尼联合 ET 治疗的患者中有 1.4%出现发热性中性粒细胞减少症。两组所有级别血液学不良事件的累积发生率在治疗的第一年达到峰值，随后在接下来的 5 年中趋于平稳。帕博西尼联合 ET 组有 13 例患者和 ET 组有 3 例患者报告间质性肺病。