Medical University of Vienna, Comprehensive Cancer Center, Vienna, Austria.
ABCSG, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.
J Clin Oncol. 2022 Jan 20;40(3):282-293. doi: 10.1200/JCO.21.02554. Epub 2021 Dec 7.
Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed.
In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer-free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival.
Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial.
At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor-positive breast cancer.
帕博西尼是一种细胞周期蛋白依赖性激酶 4 和 6 抑制剂，已被批准用于治疗晚期乳腺癌。在辅助治疗环境中，尚未确定将帕博西尼添加到激素受体阳性乳腺癌的内分泌治疗中的潜在价值。
在前瞻性、随机、III 期 PALLAS 试验中，将人表皮生长因子受体 2 阴性的激素受体阳性早期乳腺癌患者随机分配接受 2 年的帕博西尼（每日口服 125mg，28 天周期的第 1-21 天）联合辅助内分泌治疗或单独辅助内分泌治疗（至少 5 年）。该研究的主要终点是无侵袭性疾病生存（iDFS）；次要终点是无侵袭性乳腺癌生存、远处无复发生存、局部区域无复发生存和总生存。
在 3 年内，来自全球 21 个国家的 406 个中心共招募了 5796 名患者，5761 名患者被纳入意向治疗人群。在最终方案定义的分析中，中位随访 31 个月时，在接受帕博西尼联合内分泌治疗的 2884 名患者中有 253 名（8.8%）和接受内分泌治疗的 2877 名患者中有 263 名（9.1%）发生 iDFS 事件，两组之间的结果相似（4 年 iDFS：84.2% 84.5%；风险比，0.96；95%CI，0.81 至 1.14； =.65）。次要时间事件终点无显著差异，亚组分析也未显示任何亚组差异。该试验中帕博西尼没有新的安全性信号。
在 PALLAS 试验的最终分析中，与单独内分泌治疗相比，在早期激素受体阳性乳腺癌患者中，辅助应用帕博西尼并未改善结局。
