来曲唑联合帕博西尼治疗雌激素受体阳性、人表皮生长因子受体 2 阴性的晚期乳腺癌患者：来自 PALOMA-2 研究的日本患者亚组分析。

Palbociclib in combination with letrozole in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: PALOMA-2 subgroup analysis of Japanese patients.

机构信息

Division of Breast and Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.

National Cancer Center Hospital, Tokyo, Japan.

出版信息

Int J Clin Oncol. 2019 Mar;24(3):274-287. doi: 10.1007/s10147-018-1353-9. Epub 2018 Dec 4.

BACKGROUND

In PALOMA-2, palbociclib-letrozole significantly improved progression-free survival (PFS) vs placebo-letrozole in women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (ABC) in the first-line setting. We evaluated the efficacy, safety, and pharmacokinetics of palbociclib in Japanese women in PALOMA-2.

METHODS

In this phase 3 study, 666 postmenopausal women with ER+/HER2- ABC were randomized 2:1 to palbociclib (125 mg/day [3 weeks on/1 week off]) plus letrozole (2.5 mg daily) or placebo plus letrozole. A prespecified, exploratory, subgroup analysis of Japanese patients (n = 46) was conducted to compare results with those of the overall population.

RESULTS

At the February 26, 2016 cutoff, median PFS among the 46 Japanese patients was 22.2 months (95%CI, 13.6‒not estimable) with palbociclib-letrozole vs 13.8 months (5.6‒22.2) with placebo-letrozole (hazard ratio, 0.59 [95%CI, 0.26-1.34]). The most common adverse events (AEs) were hematologic and more frequent among Japanese patients than the overall population (neutropenia: 93.8% [87.5% grade 3/4] vs 79.5% [66.4%]; leukopenia: 62.5% [43.8%] vs 39.0% [24.8%]); no Japanese patients had febrile neutropenia. Palbociclib dose reductions due to toxicity (mainly neutropenia) were more common in Japanese patients (62.5% vs 36.0%); few permanently discontinued due to AEs. Although mean palbociclib trough concentration was higher in Japanese patients vs non-Asians (95.4 vs 61.7 ng/mL), the range of individual values of the Japanese patients was within that of non-Asians.

CONCLUSIONS

These results from PALOMA-2 suggest that palbociclib-letrozole merits consideration as a first-line treatment option for postmenopausal Japanese patients with ER+/HER2‒ ABC. ClinicalTrials.gov: NCT01740427.

背景

在 PALOMA-2 研究中，与安慰剂联合来曲唑相比，哌柏西利联合来曲唑显著改善了雌激素受体阳性、人表皮生长因子受体 2 阴性（ER+/HER2-）的晚期乳腺癌（ABC）患者的无进展生存期（PFS）。我们评估了哌柏西利在 PALOMA-2 中日本女性中的疗效、安全性和药代动力学。

方法

这是一项 3 期研究，666 例绝经后 ER+/HER2-ABC 患者按 2:1 的比例随机分配至哌柏西利（125mg/天[3 周用药/1 周停药]）联合来曲唑（2.5mg 每日）或安慰剂联合来曲唑。对日本患者（n=46）进行了预设的探索性亚组分析，以比较与总体人群的结果。

结果

截至 2016 年 2 月 26 日，哌柏西利联合来曲唑组的 46 例日本患者的中位 PFS 为 22.2 个月（95%CI，13.6-不可评估），而安慰剂联合来曲唑组为 13.8 个月（5.6-22.2）（风险比，0.59[95%CI，0.26-1.34]）。最常见的不良事件（AE）是血液学的，且在日本患者中比总体人群更常见（中性粒细胞减少：93.8%[87.5%为 3/4 级] vs 79.5%[66.4%]；白细胞减少：62.5%[43.8%] vs 39.0%[24.8%]）；无日本患者发生发热性中性粒细胞减少症。由于毒性（主要为中性粒细胞减少症），哌柏西利剂量减少在日本患者中更为常见（62.5% vs 36.0%）；少数患者因 AE 永久停药。虽然日本患者的平均哌柏西利谷浓度高于非亚洲人（95.4 vs 61.7ng/mL），但日本患者个体值的范围在非亚洲人范围内。