一线CDK4/6抑制剂治疗后转移性激素受体阳性、人表皮生长因子受体2阴性乳腺癌患者化疗选择的预后影响

Prognostic impact of the choice of chemotherapy after first-line CDK4/6 inhibitor therapy in patients with metastatic hormone receptor-positive, HER2-negative breast cancer.

作者信息

Michel Laura L, Ziegler Philipp, Kreis Philipp, Hartkopf Andreas D, Wallwiener Markus, Häberle Lothar, John Nelson, Kolberg Hans-Christian, Hadji Peyman, Tesch Hans, Ettl Johannes, Lüftner Diana, Müller Volkmar, Belleville Erik, Wimberger Pauline, Enzinger Hans-Martin, Huebner Hanna, Uhrig Sabrina, Hack Carolin C, Krabisch Petra, Fasching Peter A, Wuerstlein Rachel, Untch Michael, Ditsch Nina, Hein Alexander, Janni Wolfgang, Taran Florin-Andrei, Lux Michael P, Wallwiener Diethelm, Brucker Sara Y, Fehm Tanja N, Schneeweiss Andreas, Goossens Chloë, Engler Tobias

机构信息

National Center for Tumor Diseases, Heidelberg University Hospital, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Comprehensive Cancer Center Erlangen-EMN (CCC-EMN), Erlangen, Germany.

出版信息

Eur J Cancer. 2025 Sep 9;227:115689. doi: 10.1016/j.ejca.2025.115689. Epub 2025 Aug 5.

DOI:10.1016/j.ejca.2025.115689

PMID:40780076

Abstract

INTRODUCTION

Whereas CDK4/6 inhibitors (CDK4/6i) are the standard first-line therapy for patients with hormone receptor-positive (HRpos), HER2-negative (HER2neg) metastatic breast cancer, guidelines on treatment options after progression on CDK4/6i are more diverse. Chemotherapy is recommended if a patient develops endocrine resistance or experiences a visceral crisis. However, the impact of the choice of chemotherapy remains unknown.

METHODS

HRpos/HER2neg patients who received first-line CDK4/6i, followed by second-line chemotherapy (N = 215) were selected from the prospective PRAEGNANT registry (NCT02338167). Cox regression analyses were used to evaluate the correlation between the choice of chemotherapy (capecitabine monotherapy, capecitabine + bevacizumab, taxane monotherapy, taxane + bevacizumab, anthracycline, other chemotherapeutics) and progression-free survival (PFS) and overall survival (OS).

RESULTS

Patients who received second-line chemotherapy mostly had high-grade tumors (G2: 62.3 %, G3: 33.3 %), visceral metastases (62.3 %) and developed metastatic disease following a primary breast cancer diagnosis (73.8 %). Capecitabine was the most common regimen (25.1 %), followed by taxane + bevacizumab (17.2 %). When adjusting for other prognostic factors (age, BMI, grading, ECOG, metastasis group and time to metastases), the choice of chemotherapy did not influence PFS (p = 0.16) nor OS (p = 0.47). Adjusted hazard ratios for PFS were lowest in regimens with bevacizumab (capecitabine as reference; capecitabine + bevacizumab: 0.53 (95 %CI: 0.29, 0.97); taxane + bevacizumab: 0.64 (95 %CI 0.35, 1.15)).

CONCLUSION

Although the choice of chemotherapy post-CDK4/6i did not significantly affect PFS or OS, combinations with bevacizumab may have some benefit. Nevertheless, considering side effects may be most important when choosing the type of second-line chemotherapy.

摘要

引言

虽然细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）是激素受体阳性（HRpos）、人表皮生长因子受体2阴性（HER2neg）转移性乳腺癌患者的标准一线治疗方案，但关于CDK4/6i治疗进展后的治疗选择指南则更为多样。如果患者出现内分泌抵抗或发生内脏危象，则推荐进行化疗。然而，化疗选择的影响尚不清楚。

方法

从前瞻性PRAEGNANT注册研究（NCT02338167）中选取接受一线CDK4/6i治疗，随后接受二线化疗的HRpos/HER2neg患者（N = 215）。采用Cox回归分析评估化疗选择（卡培他滨单药治疗、卡培他滨+贝伐单抗、紫杉烷单药治疗、紫杉烷+贝伐单抗、蒽环类药物、其他化疗药物）与无进展生存期（PFS）和总生存期（OS）之间的相关性。

结果

接受二线化疗的患者大多患有高级别肿瘤（G2：62.3%，G3：33.3%）、内脏转移（62.3%），且在原发性乳腺癌诊断后发生转移性疾病（73.8%）。卡培他滨是最常用的方案（25.1%），其次是紫杉烷+贝伐单抗（17.2%）。在调整其他预后因素（年龄、体重指数、分级、美国东部肿瘤协作组体能状态评分、转移组和转移时间）后，化疗选择对PFS（p = 0.16）和OS（p = 0.47）均无影响。含贝伐单抗方案的PFS调整后风险比最低（以卡培他滨为参照；卡培他滨+贝伐单抗：0.53（95%置信区间：0.29，0.97）；紫杉烷+贝伐单抗：0.64（95%置信区间0.35，1.15））。