Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Breast Cancer Res Treat. 2020 Aug;183(1):107-116. doi: 10.1007/s10549-020-05750-y. Epub 2020 Jun 23.
Neutropenia is the most common toxicity of CDK4/6 inhibitors, causing frequent dose interruptions. However, CDK4/6 inhibitor-induced neutropenia shows a benign clinical course in contrast to that caused by chemotherapy. Here, we investigated the safety of a new dose scheme for palbociclib, which avoids dose delays or reductions due to afebrile grade 3 neutropenia.
A consecutive cohort of ER( +)/HER2( -) advanced breast cancer patients who received palbociclib between 2017 and 2018 was analyzed. The patients were classified into Group 1 (patients who maintained palbociclib dose with afebrile grade 3 neutropenia), Group 2 (patients who experienced any dose modification with afebrile grade 3 neutropenia), and Group 3 (patients without afebrile grade 3 neutropenia). The primary endpoint was febrile neutropenia incidence; other toxicities were compared with those of the PALOMA-2 trial.
Among the 107 patients, 54.2%, 22.4%, and 23.4% were classified into Groups 1, 2, and 3, respectively. There was no febrile neutropenia in Groups 1 and 2 during palbociclib treatment. Group 1 showed higher incidence of thrombocytopenia (all-grade, 32.8%; grade 3-4, 8.6%) than Group 2 and the PALOMA-2 data, but there was no bleeding related to thrombocytopenia. Group 1 showed higher incidence of all-grade non-hematologic adverse events than Group 2; only one grade 3 non-hematologic toxicity was observed in Group 1. There were no treatment-related hospitalizations or deaths in Group 1.
Thus, omitting palbociclib dose modification with afebrile grade 3 neutropenia is safe and tolerable without febrile neutropenia events. This scheme could be useful to avoid unnecessary reductions in palbociclib doses in future practice.
CDK4/6 抑制剂引起的中性粒细胞减少是最常见的毒性反应，导致频繁的剂量中断。然而，与化疗引起的中性粒细胞减少相比，CDK4/6 抑制剂引起的中性粒细胞减少具有良性的临床过程。在这里，我们研究了一种新的帕博西尼剂量方案的安全性，该方案避免了因无发热性 3 级中性粒细胞减少而延迟或减少剂量。
对 2017 年至 2018 年间接受帕博西尼治疗的连续队列的 ER(+) / HER2(-) 晚期乳腺癌患者进行了分析。患者被分为 1 组（中性粒细胞减少症 3 级且无发热的患者维持帕博西尼剂量）、2 组（中性粒细胞减少症 3 级且无发热但接受任何剂量调整的患者）和 3 组（无发热性 3 级中性粒细胞减少症的患者）。主要终点是发热性中性粒细胞减少症的发生率；其他毒性反应与 PALOMA-2 试验进行了比较。
在 107 例患者中，54.2%、22.4%和 23.4%分别归入 1 组、2 组和 3 组。在帕博西尼治疗期间，1 组和 2 组均未发生发热性中性粒细胞减少症。1 组血小板减少症的发生率高于 2 组和 PALOMA-2 数据（所有级别，32.8%；3-4 级，8.6%），但无血小板减少相关出血。1 组全级别非血液学不良事件的发生率高于 2 组；1 组仅观察到 1 例 3 级非血液学毒性。1 组无治疗相关住院或死亡。
因此，在无发热性 3 级中性粒细胞减少症的情况下，不调整帕博西尼剂量是安全且可耐受的，无发热性中性粒细胞减少症发生。在未来的实践中，这种方案可以避免不必要的帕博西尼剂量减少。
