桓兴医讯

北京桓兴医院,桓兴医院,桓兴肿瘤医院

推荐文章

您当前位置:桓兴肿瘤医院 > 桓兴医讯 > 桓兴医讯 在三阴性乳腺癌的标准新辅助化疗中加入PARP抑制剂维拉
桓兴医讯 在三阴性乳腺癌的标准新辅助化疗中加入PARP抑制剂维拉
文章来源:北京市朝阳区桓兴肿瘤医院 点击数: 发布时间:2019-08-06 14:34
《柳叶刀肿瘤分册》2018年2月28日在线先发
在三阴性乳腺癌的标准新辅助化疗中加入PARP抑制剂维拉帕尼和卡铂或只加入卡铂((BrighTNess试验):一项随机3期试验
背景
虽然三阴性乳腺癌的几项随机试验表明,新辅助化疗中加入卡铂,加或不加多聚(ADP-核糖)聚合酶(PARP)抑制剂能增加达到病理完全缓解的可能性,但这些治疗方法的使用一直存在争议。BrighTNess试验旨在评估三阴性乳腺癌标准新辅助化疗中加入PARP抑制剂和卡铂或仅加入卡铂的疗效。
方法
我们在15个国家的145个医疗点进行了一项3期、随机、双盲、安慰剂对照试验(BrighTNess试验)。根据交互式应答技术系统,通过数字区块(区块大小为4)、亚组分层,将≥18岁、组织学或细胞学证实为临床II-III期、适合进行根治性手术、ECOG评分0-1分的三阴性乳腺癌初治患者随机分组(2:1:1),接受第1个阶段的三种治疗方案之一的治疗:紫杉醇(80mg/m2静脉滴注,每周1次,共12次)+卡铂(AUC,6mg/mL/分钟,静脉滴注每3周1次,共4个周期)+维拉帕尼(50mg口服,每日2次);紫杉醇+卡铂+维拉帕尼安慰剂(每日2次);或者紫杉醇+卡铂安慰剂(每3周1次,4个周期)+维拉帕尼安慰剂。第1个阶段治疗后,将所有患者分配到第2个阶段,每2-3周接受1次阿霉素和环磷酰胺治疗,4个周期。根据BRCA基因状态、淋巴结分期、阿霉素和环磷酰胺使用计划安排,对第1个阶段进行随机化亚组分层。主要终点是新辅助治疗完成后,由医疗点的病理医生确定的乳腺和淋巴结的病理完全缓解。采用意向性治疗进行疗效分析,安全性分析纳入了接受过至少一个研究治疗剂量的所有患者。这些是这项仍在进行中的临床试验的首个结果,用于本文分析的数据锁定日期是2016年12月8日。这项研究已在ClinicalTrials.gov注册,注册号NCT02032277。
发现
2014年4月4日至2016年3月18日,对634名患者进行了随机分组:316名到紫杉醇+卡铂+维拉帕尼组,160名到紫杉醇+卡铂组,158名到紫杉醇单药组。紫杉醇+卡铂+维拉帕尼组获得病理完全缓解的患者比例高于紫杉醇单药组(316名患者中有168名[53%],对比158名患者中有49名[31%],p<0.0001),但未高于紫杉醇+卡铂组(160名患者中有92名[58%],p=0.36)。接受卡铂治疗的患者,3、4级毒性和严重的不良反应更常见,而维拉帕尼没有大幅增加毒性。总体上,整个完整治疗期间最常见的3、4级事件为中性粒细胞减少(628名患者中有352名[56%])、贫血(180名[29%])、血小板减少(75名[12%]),第2个阶段期间为中性粒细胞减少性发热(601名患者中有88名[15%])。最常见的严重不良事件是中性粒细胞减少性发热(628名患者中有80名[13%])和贫血(20名[3%])。
解释
虽然紫杉醇方案加入维拉帕尼和卡铂,并序贯阿霉素和环磷酰胺提高了三阴性乳腺癌患者获得病理完全缓解的比例,但卡铂和紫杉醇方案中加入维拉帕尼没有(进一步)提高三阴性乳腺癌患者获得病理完全缓解的比例。紫杉醇方案中加入卡铂(加或不加维拉帕尼)所增加的毒性可控,没有明显影响紫杉醇序贯阿霉素和环磷酰胺的治疗。鉴于与既往研究结果一致,对于高危三阴性乳腺癌,加入卡铂会有良好的风险获益,可以考虑将卡铂作为新辅助化疗的一个有潜力的组成部分。
北京市朝阳区桓兴肿瘤医院 桓兴医讯编译组 王津京
2019年8月6日 星期二
Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial
DOI: https://doi.org/10.1016/S1470-204http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30111-6/fulltext 5(18)30111-6
Background
Although several randomised trials in patients with triple-negative breast cancer have shown that the addition of carboplatin, with or without poly(ADP-ribose) polymerase (PARP) inhibitors, to neoadjuvant chemotherapy increases the likelihood of achieving a pathological complete response, the use of these therapies in this setting has remained controversial. The BrighTNess trial was designed to assess the addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer.
Methods
We did a phase 3, randomised, double-blind, placebo-controlled trial (BrighTNess) across 145 sites in 15 countries. Patients aged 18 years and older with previously untreated histologically or cytologically confirmed clinical stage II–III triple-negative breast cancer, who were candidates for potentially curative surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1, were randomly assigned (2:1:1) by an interactive response technology system via permuted blocks (block size of four) within strata to receive one of three segment 1 regimens: paclitaxel (80 mg/m2 intravenously weekly for 12 doses) plus carboplatin (area under the curve 6 mg/mL per min, intravenously every 3 weeks, for four cycles) plus veliparib (50 mg orally, twice a day); paclitaxel plus carboplatin plus veliparib placebo (twice a day); or paclitaxel plus carboplatin placebo (every 3 weeks for four cycles) plus veliparib placebo. Following segment 1, all patients were assigned to segment 2 in which they received doxorubicin and cyclophosphamide every 2–3 weeks for four cycles. Randomisation for segment 1 was stratified by germline BRCA mutation status, nodal stage, and planned schedule of doxorubicin and cyclophosphamide administration. The primary endpoint was pathological complete response in breast and lymph nodes as determined by site pathologists following completion of neoadjuvant therapy. Efficacy analyses were done by intention to treat and safety analyses included all patients who received at least one dose of study treatment. These are the first results of an ongoing clinical trial; the data cutoff for the analyses presented was Dec 8, 2016. This study is registered with ClinicalTrials.gov, number NCT02032277.
Findings
Between April 4, 2014, and March 18, 2016, 634 patients were randomly assigned: 316 to paclitaxel plus carboplatin plus veliparib, 160 to paclitaxel plus carboplatin, and 158 to paclitaxel alone. The proportion of patients who achieved a pathological complete response was higher in the paclitaxel, carboplatin, and veliparib group than in patients receiving paclitaxel alone (168 [53%] of 316 patients vs 49 [31%] of 158, p<0·0001), but not compared with patients receiving paclitaxel plus carboplatin (92 [58%] of 160 patients, p=0·36). Grade 3 or 4 toxicities, and serious adverse events were more common in patients receiving carboplatin, whereas veliparib did not substantially increase toxicity. The most common grade 3 or 4 events overall were neutropenia (352 [56%] of 628 patients), anaemia (180 [29%]), and thrombocytopenia (75 [12%]) through complete treatment, and febrile neutropenia (88 [15%] of 601 patients) during segment 2. The most common serious adverse events were febrile neutropenia (80 [13%] of 628 patients) and anaemia (20 [3%]).
Interpretation
Although the addition of veliparib and carboplatin to paclitaxel followed by doxorubicin and cyclophosphamide improved the proportion of patients with triple-negative breast cancer who achieved a pathological complete response, the addition of veliparib to carboplatin and paclitaxel did not. Increased toxicities with the addition of carboplatin (with or without veliparib) to paclitaxel were manageable and did not substantially affect treatment delivery of paclitaxel followed by doxorubicin and cyclophosphamide. Given the consistent results with previous studies, the addition of carboplatin appears to have a favourable risk to benefit profile and might be considered as a potential component of neoadjuvant chemotherapy for patients with high-risk, triple-negative breast cancer.

标签:

北京桓兴肿瘤医院,北京朝阳区桓兴肿瘤医院,桓兴肿瘤医院,北京桓兴医院,北京专科肿瘤医院 北京桓兴肿瘤医院,北京朝阳区桓兴肿瘤医院,桓兴肿瘤医院,北京桓兴医院,北京专科肿瘤医院