PALLAS试验（ABCSG-42/AFT-05/PrE0109/BIG-14-13）中IIA期与IIB/III期的结果。
Outcomes in stage IIA versus stage IIB/III in the PALLAS trial [ABCSG-42/AFT-05/PrE0109/BIG-14-13]).
作者信息
DeMichele A, Dueck A C, Hlauschek D, Martin M, Burstein H, Pfeiler G, Zdenkowski N, Wolff A, Bellet-Ezquerra M, Winer E, Balic M, Miller K, Colleoni M, Lake D, Rubovsky G, Cameron D, Balko J, Singer C F, Nowecki Z, Iwata H, Wolmark N, Parraga K A, Rugo H, Steger G G, Traina T, Werutsky G, Czajkowska D, Metzger O, El-Abed S, Theall K P, Lu R D, O'Brien P, Fesl C, Mayer E, Gnant M
机构信息
Department of Hematology and Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania, Room 10-153, 3400 Civic Center Blvd., Philadelphia, PA, 19104, USA.
ECOG-ACRIN Cancer Research Group, Philadelphia, PA, USA.
出版信息
Breast Cancer Res. 2025 Jan 23;27(1):12. doi: 10.1186/s13058-024-01941-3.
BACKGROUND
The PALLAS trial investigated the addition of palbociclib to standard adjuvant endocrine therapy to reduce breast cancer recurrence. This pre-specified analysis was conducted to determine whether adjuvant palbociclib benefited patients diagnosed with lower risk stage IIA disease compared to those with higher stage disease.
METHODS
PALLAS was an international, multicenter, randomized, open-label, phase III trial, representing a public-private partnership between Pfizer, the Austrian Breast Cancer Study Group, and the U.S. ALLIANCE Foundation. Patients diagnosed with stage II-III, hormone-receptor-positive, HER2/neu negative breast cancer within 12 months of diagnosis had completed all definitive therapy aside from endocrine therapy (started within 6 months prior to study entry) were eligible. All patients were required to submit a formalin-fixed paraffin-embedded (FFPE) tumor block. Patients were randomly assigned 1:1 to receive standard adjuvant endocrine therapy (of physicians' choice) for at least 5 years with or without 2 years of palbociclib, administered orally at a starting dose of 125 mg daily, given for 21 days followed by a 7-day break.
RESULTS
A total of 5,796 patients with HR + /HER2- early breast cancer (including 1,010 with stage IIA) were enrolled. Median follow-up was 50 months for stage IIA patients and 43.1 months overall. In the stage IIA cohort, 4-year iDFS in the palbociclib arm was 92.9% versus 92.1% for ET alone (HR 0.75, 95%CI 0.48-1.19, p = 0.23). There was no differential benefit by histologic grade, chemotherapy receipt, age, or anatomic/clinical risk. Additionally, no benefit to palbociclib was seen in this cohort in invasive breast cancer-free survival (iBCFS), locoregional relapse-free survival (LRFS), distant relapse-free survival (DRFS), or overall survival (OS). For the stage IIB/III patients, 4-year iDFS was 85.3% for palbociclib + ET versus 83.6% for ET alone (HR 0.91, 95% CI 0.77-1.07, p = 0.24).
CONCLUSIONS AND RELEVANCE
While there were substantial differences in outcome for stage IIA versus IIB/III patients at 4 years of follow-up, the addition of 2 years of palbociclib did not improve outcomes for patients, regardless of stage.
TRIAL REGISTRATION
ClinicalTrials.gov number NCT02513394 Registered 30 Jul 2015.
背景
PALLAS试验研究了在标准辅助内分泌治疗基础上加用帕博西尼以降低乳腺癌复发风险。进行这项预先设定的分析是为了确定与疾病分期较高的患者相比，辅助性帕博西尼对诊断为低风险IIA期疾病的患者是否有益。
方法
PALLAS是一项国际多中心、随机、开放标签的III期试验，是辉瑞公司、奥地利乳腺癌研究组和美国联盟基金会之间的公私合作项目。诊断为II-III期、激素受体阳性、HER2/neu阴性乳腺癌且在诊断后12个月内完成除内分泌治疗（在研究入组前6个月内开始）之外的所有确定性治疗的患者符合条件。所有患者均需提交福尔马林固定石蜡包埋（FFPE）肿瘤块。患者按1:1随机分配，接受标准辅助内分泌治疗（由医生选择）至少5年，同时接受或不接受2年的帕博西尼治疗，帕博西尼口服起始剂量为每日125mg，服用21天，随后休息7天。
结果
共纳入5796例HR+/HER2-早期乳腺癌患者（包括1010例IIA期患者）。IIA期患者的中位随访时间为50个月，总体中位随访时间为43.1个月。在IIA期队列中，帕博西尼组的4年无浸润性疾病生存率（iDFS）为92.9%，单纯内分泌治疗组为92.1%（风险比[HR]0.75，95%置信区间[CI]0.48-1.19，p=0.23）。在组织学分级、是否接受化疗、年龄或解剖/临床风险方面没有差异获益。此外，在该队列中，帕博西尼在无浸润性乳腺癌生存率（iBCFS）､无局部区域复发生存率（LRFS）､无远处复发生存率（DRFS）或总生存率（OS）方面均未显示出获益。对于IIB/III期患者，帕博西尼联合内分泌治疗组的4年iDFS为85.3%，单纯内分泌治疗组为83.6%（HR 0.91，95%CI 0.77-1.07，p=0.24）。
结论及意义
虽然IIA期与IIB/III期患者在4年随访时的结果存在显著差异，但无论疾病分期如何，加用2年的帕博西尼均未改善患者的预后。
试验注册
ClinicalTrials.gov编号NCT02513394，于2015年7月30日注册。
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