单用辅助性贝伐单抗联合节拍化疗或标准剂量化疗优化残留乳腺癌的新辅助治疗后方案：DFCI 05-055和DFCI 09-134/TBCRC 012/ABCDE临床试验的联合分析
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.
作者信息
Trapani Dario, Jin Qingchun, Miller Kathy D, Rugo Hope S, Reeder-Hayes Katherine E, Traina Tiffany, Abdou Yara, Falkson Carla, Abramson Vandana, Ligibel Jennifer, Chen Wendy, Come Steven, Nohria Anju, Ryabin Nicole, Tayob Nabihah, Tolaney Sara M, Burstein Harold J, Mayer Erica L
机构信息
Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA; Harvard Medical School, Boston, MA.
Data Science, Dana-Farber Cancer Institute, Boston, MA.
出版信息
Clin Breast Cancer. 2025 Jun;25(4):e419-e430.e5. doi: 10.1016/j.clbc.2024.12.018. Epub 2024 Dec 31.
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).
背景
新辅助治疗后仍有残留病灶的乳腺癌患者复发风险增加。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）为新辅助化疗后有残留病灶的I - III期乳腺癌患者提供基于贝伐单抗的辅助治疗。研究05 - 055评估了四种治疗方案：贝伐单抗（A组）；贝伐单抗联合小剂量环磷酰胺和甲氨蝶呤（CM）（B组）；贝伐单抗联合按体表面积给药的卡培他滨（C组）；或固定剂量卡培他滨（D组）。主要终点是可行性和耐受性。在09 - 134研究中，患者被随机分为接受或不接受CM联合贝伐单抗治疗；主要终点是无复发生存期（RFS）。09 - 134研究因入组不足而提前结束。对来自05 - 055和09 - 134的参与者进行了汇总生存分析。
结果
在总共213例患者中（05 - 055，n = 163；09 - 134，n = ），任何级别的最常见不良事件（AE）是头痛（49.3%）和疲劳（57.3%）。3 - 4级AE在C组（71.4%）和D组（72.5%）中最高。贝伐单抗单药治疗的36个月RFS为58.0%，贝伐单抗加CM为62.3%，贝伐单抗加卡培他滨为72.7% - 75.0%（取决于给药方案）。在三阴性乳腺癌（TNBC）中，卡培他滨治疗与改善RFS独立相关（HR：0.47；95%CI，0.23 - 0.96）。
结论
这项汇总分析表明，新辅助治疗后使用贝伐单抗加卡培他滨可能与改善RFS相关，尤其是在TNBC中。每种方案都有中度毒性，尽管进行了这些治疗，新辅助治疗后仍有残留病灶的患者复发率仍然很高，这表明需要新的策略。
临床试验注册
clinicaltrials.gov，NCT00121134（DFCI方案编号：05 - 055）；NCT00925652（DFCI方案编号：09 - 134）。 （注：原文中09 - 134的患者数量“n = ”处信息缺失）
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