Chalumeau Clelia, Carton Matthieu, Eeckhoutte Alexandre, Ballet Stelly, Vincent-Salomon Anne, Vuagnat Perrine, Bellesoeur Audrey, Pierga Jean-Yves, Stern Marc-Henri, Bidard Francois-Clement, Lerebours Florence
Department of Medical Oncology, Institut Curie, 92210 St Cloud, France.
Biostatistics, Institut Curie, 75005 Paris, France.
Cancers (Basel). 2022 Apr 24;14(9):2114. doi: 10.3390/cancers14092114.
The and genes are co-amplified in about 40% of HER2 positive (HER2+) breast cancers. Oral etoposide (VP16), an inhibitor of topoisomerase-II (encoded by ), has demonstrated clinical activity in metastatic breast cancer (MBC). The benefit of oral VP16 combined with trastuzumab (VP16-T) in HER2+ MBC has not yet been evaluated.
Patients treated at the Institut Curie Hospitals with VP16-T for HER2+ MBC were retrieved by an in silico search. Progression-free survival (PFS), overall survival (OS), response rate, prolonged PFS (defined as at least 6 months), clinical benefit, and toxicity were assessed. The co-amplification of and was assessed by shallow whole genome sequencing on tumor tissue whenever available.
Forty-three patients received VP16-T after a median number of six prior treatment lines for HER2+ MBC. Median PFS and OS were 2.9 months (95% CI [2.4-4.7]) and 11.3 months (95% CI [8.3-25.0]), respectively. Three patients had a complete response, while 12/40 (30%) experienced clinical benefit. Only three patients stopped treatment for toxicity. Seven (35%) patients displayed a co-amplification. No statistically significant correlation was found between outcome and co-amplification.
Our analysis suggests a favorable efficacy and toxicity profile for VP16-T in patients with heavily pretreated HER2+ MBC.
在约40%的人表皮生长因子受体2阳性（HER2+）乳腺癌中，和基因会共同扩增。口服依托泊苷（VP16）是一种拓扑异构酶II（由编码）抑制剂，已在转移性乳腺癌（MBC）中显示出临床活性。口服VP16联合曲妥珠单抗（VP16-T）在HER2+MBC中的益处尚未得到评估。
通过计算机检索，找出在居里研究所医院接受VP16-T治疗的HER2+MBC患者。评估无进展生存期（PFS）、总生存期（OS）、缓解率、延长的PFS（定义为至少6个月）、临床获益和毒性。只要有肿瘤组织，就通过浅层全基因组测序评估和的共同扩增情况。
43例患者在接受中位数为6线的HER2+MBC先前治疗后接受了VP16-T治疗。中位PFS和OS分别为2.9个月（95%CI[2.4-4.7]）和11.3个月（95%CI[8.3-25.0]）。3例患者完全缓解，而12/40（30%）例患者有临床获益。只有3例患者因毒性停止治疗。7例（35%）患者显示有共同扩增。在结局与共同扩增之间未发现统计学上的显著相关性。
我们的分析表明，VP16-T对预处理严重的HER2+MBC患者具有良好的疗效和毒性特征。
