Optimizing Postneoadjuvant Treatment of Residual Breast Cancer With Adjuvant Bevacizumab Alone, With Metronomic or Standard-Dose Chemotherapy: A Combined Analysis of DFCI 05-055 and DFCI 09-134/TBCRC 012/ABCDE Clinical Trials.

IF 2.9 3区医学 Q2 ONCOLOGY

Clinical breast cancer Pub Date : 2024-12-31 DOI:10.1016/j.clbc.2024.12.018

Dario Trapani, Qingchun Jin, Kathy D Miller, Hope S Rugo, Katherine E Reeder-Hayes, Tiffany Traina, Yara Abdou, Carla Falkson, Vandana Abramson, Jennifer Ligibel, Wendy Chen, Steven Come, Anju Nohria, Nicole Ryabin, Nabihah Tayob, Sara M Tolaney, Harold J Burstein, Erica L Mayer

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引用次数: 0

Abstract

Background: Breast cancer patients with residual disease after neoadjuvant therapy have increased risk of recurrence. Novel therapies to decrease this risk are urgently needed.

Methods: Two clinical trials (05-055 and 09-134) offered adjuvant bevacizumab-based therapy to stage I-III breast cancer patients with residual disease after neoadjuvant chemotherapy. Study 05-055 evaluated four treatment regimens: bevacizumab (cohort A); bevacizumab with metronomic cyclophosphamide and methotrexate (CM) (cohort B); and bevacizumab with body surface area-dosed capecitabine (cohorts C); or flat-dosed capecitabine (cohort D). The primary endpoint was feasibility and tolerability. In 09-134, patients were randomized to bevacizumab with or without CM; the primary endpoint was recurrence-free survival (RFS). Study 09-134 closed prematurely for lack of accrual. A pooled survival analysis with participants from 05-055 and 09-134 was conducted.

Results: Among 213 total patients (05-055, n = 163; 09-134, n = 50), the most common adverse events (AEs) of any grade were headache (49.3%) and fatigue (57.3%). Grade 3-4 AEs were highest in cohorts C (71.4%) and D (72.5%). The 36-month RFS was 58.0% with bevacizumab monotherapy, 62.3% with bevacizumab plus CM, and 72.7%-75.0% with bevacizumab plus capecitabine (depending on schedule). Treatment with capecitabine was independently associated with improved RFS in triple-negative breast cancer (TNBC) (HR: 0.47; 95% CI, 0.23-0.96).

Conclusion: This pooled analysis demonstrates that postneoadjuvant bevacizumab plus capecitabine may be associated with improved RFS, especially in TNBC. Each regimen carries moderate toxicity, and despite these treatments, patients with residual disease after neoadjuvant therapy still experience high rates of recurrence, indicating that new strategies are warranted.

Clinical trial registration: clinicaltrials.gov, NCT00121134 (DFCI Protocol Number: 05-055); NCT00925652 (DFCI Protocol Number: 09-134).

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优化新辅助后残余乳腺癌使用贝伐单抗辅助治疗、节拍或标准剂量化疗：DFCI 05-055和DFCI 09-134/TBCRC 012/ABCDE临床试验的综合分析

背景：乳腺癌患者在新辅助治疗后残留病变的复发风险增加。迫切需要新的治疗方法来降低这种风险。方法：两项临床试验（05-055和09-134）对新辅助化疗后残留病变的I-III期乳腺癌患者进行以贝伐单抗为基础的辅助治疗。研究05-055评估了四种治疗方案：贝伐单抗（队列A）；贝伐单抗联合节律环磷酰胺和甲氨蝶呤（CM）（队列B）；贝伐单抗与体表剂量卡培他滨（C组）；或平剂量卡培他滨（队列D）。主要终点是可行性和耐受性。09-134年，患者随机接受贝伐单抗治疗，伴有或不伴有CM；主要终点为无复发生存期（RFS）。研究09-134因缺乏应计费用而提前结束。对05-055和09-134的参与者进行了合并生存分析。结果：213例患者中(05-055例，n = 163；09-134, n = 50)，所有级别中最常见的不良事件（ae）为头痛（49.3%）和疲劳（57.3%）。3-4级ae发生率最高的是C组（71.4%）和D组（72.5%）。贝伐单抗单药治疗的36个月RFS为58.0%，贝伐单抗联合CM组为62.3%，贝伐单抗联合卡培他滨组为72.7%-75.0%（取决于方案）。卡培他滨治疗与三阴性乳腺癌（TNBC）的RFS改善独立相关(HR: 0.47；95% ci, 0.23-0.96)。结论：本汇总分析表明，新辅助治疗后贝伐单抗联合卡培他滨可能与RFS改善相关，尤其是TNBC患者。每种方案都有中度毒性，尽管采用了这些治疗方法，但新辅助治疗后残留疾病的患者仍有很高的复发率，这表明需要新的治疗策略。临床试验注册：clinicaltrials.gov, NCT00121134 (DFCI协议号：05-055)；NCT00925652 （DFCI协议号：09-134）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical breast cancer 医学-肿瘤学

CiteScore

5.40

自引率

3.20%

发文量

174

审稿时长

48 days

期刊介绍： Clinical Breast Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of breast cancer. Clinical Breast Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of breast cancer. The main emphasis is on recent scientific developments in all areas related to breast cancer. Specific areas of interest include clinical research reports from various therapeutic modalities, cancer genetics, drug sensitivity and resistance, novel imaging, tumor genomics, biomarkers, and chemoprevention strategies.