TNBC重磅 ：IMpassion130达到共同终点OS和PFS
目录
1 事件
2 IMpassion130背景
3 友商动态
4 Atezo在TNBC的其他主要临床
1 事件
Tecentriq® (atezolizumab) 联合化疗（白蛋白结合型紫杉醇，Abraxane® [albumin-bound paclitaxel; nab-paclitaxel]）对比Abraxane®
一线治疗转移性或者不可手术的局部进展性三阴乳腺癌
ITT和PD-L1阳性的群组中，Atezo联合组的疾病恶化或者死亡的风险显著降低
内部分析中OS在PD-L1阳性的群组中也令人鼓舞
数据将会提交FDA和EMA
2 IMpassion130背景
临床设计
罗氏现在有7个Tecentriq® 治疗TNBC的三床正在进行中，IMpassion 130第三个正面TNBC的免疫治疗三期临床。
基于早期的1b数据：
Tecentriq® +Abraxane®在一线治疗TNBC中有46%的ORR;
不管PD-L1表达情况，都能观察到应答
应答的患者有着高基线的肿瘤浸润性淋巴细胞（TIL），可能以此作为marker
安全性数据：无单药相关的异常不良事件
3 友商动态
友商类似的临床进展最快的是pembro的KEYNOTE-355，基于KEYNOTE-012（注意这是pembro单药，非联合）的1b数据
KEYNOTE-355 (NCT02819518) is a global phase III study of pembro+chemo vs PBO+chemo in pts with previously untreated, locally recurrent, inoperable TNBC/mTNBC.
Methods:
Eligible pts are ≥18 y and have centrally confirmed, locally recurrent, inoperable TNBC or mTNBC not previously treated with chemo (prior chemo in [neo]adjuvant setting is allowed); measurable disease per RECIST v1.1; ECOG PS 0-1; ≥6 mo between definitive surgery or last dose of adjuvant chemo, whichever was last; and first disease recurrence (≥12 mo if prior treatment with same-class agent).
先试验了联合用药的安全性：分别是pembro+白蛋白结合紫杉醇、pembro+紫杉醇、pembro+吉西他滨/卡铂
Part 1 is an open-label, unblinded safety run-in of ~30 pts in 3 arms (pembro+nab-paclitaxel, pembro+paclitaxel, pembro+gemcitabine/carboplatin).
这部分才是3期临床的主体部分
Part 2 is a double-blind, PBO-controlled study of ~828 pts randomized 2:1 to pembro 200 mg every 3 weeks + chemo (nab-paclitaxel 100 mg/m2 on d 1, 8, and 15 every 28 d; paclitaxel 90 mg/m2 on d 1, 8, and 15 every 28 d; or gemcitabine 1000 mg/m2+ carboplatin AUC 2 on d 1 and 8 every 21 d) or PBO+chemo. Crossover is not allowed. Stratification factors are study chemo (taxane vs gemcitabine/carboplatin), tumor PD-L1 expression (+/-), and prior therapy with same-class agent in the (neo)adjuvant setting (yes/no). Treatment will occur for ≤35 administrations (pembro/PBO only) or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or decision to discontinue.
主要终点：第一部分是安全性；第二部分也就是主体部分是PFS和OS，次要终点是ORR和持续缓解时间
Primary end points are safety in part 1 and PFS (by RECIST v1.1, central radiology review) and OS in part 2; secondary end points include ORR (by RECIST v1.1, central radiology review) and duration of response. AEs will be graded per NCI CTCAE v4.0. Response will be assessed at wk 8, 16, 24, then at 9-wk intervals up to 1 y, and at 12-wk intervals thereafter. Interim safety analysis will occur after pts complete 1 treatment cycle in part 1. Clinical trial information: NCT02819518.
4 Atezo在TNBC的其他主要临床
130和131分别是Atezo联合白蛋白结合型紫杉醇和普通紫杉醇一线治疗转移型TNBC的3期，但他们排除了化疗后疾病进展小于12个月的早期乳腺癌
132主要比较Atezo联合化药对比化药治疗先前化疗后疾病进展<12个月的早期乳腺癌患者，试验中选用的化药为2类非紫杉醇类药物
早期TNBC的辅助治疗：IMpassion 031
TNBC的特征是肿瘤浸润的免疫细胞（IC）表达PD-L1、高水平TILs和相比其他乳腺癌更高的突变率，可能对于免疫检测点拮抗剂来说是治疗机会。TNBC is characterized by PD-L1 expression on tumor-infiltrating immune cells (IC), high levels of tumor-infiltrating lymphocytes (TILs), and a higher mutation rate compared with other breast cancers suggesting a therapeutic opportunity for atezolizumab. Atezolizumab alone and in combination with nab-paclitaxel is well tolerated, with promising clinical activity in metastatic TNBC. Furthermore, cytotoxic chemotherapies like nab-paclitaxel can enhance anti-tumor immune responses via neoantigen release（细胞毒性药物有可能释放新生抗原提升抗肿瘤免疫）. Taken together, this supports the investigation of atezolizumab in combination with nab-paclitaxel in early-stage TNBC.
IMpassion031 is a global Phase III, double-blind, randomized, multicenter, placebo-controlled study being conducted to evaluate the efficacy and safety of neoadjuvant treatment with nab-paclitaxel → doxorubicin + cyclophosphamide and either atezolizumab or placebo in invasive stage II/III early TNBC（II/III 侵染期的早期乳腺癌）. The selection and sequence of chemotherapy has been chosen to maximize the opportunity for a robust immune response（化疗药的选择顺序用来最大化的加强免疫应答）.
术后治疗组Atezo单药维持
这个试验和KEYNOTE-522类似