以曲妥珠单抗（T）为基础的新辅助化疗对HER2阳性乳腺癌（HER2+BC）患者的病理完全缓解（pCR）率可达〜50％，从而允许进行频繁的保守手术。临床前数据和临床数据支持贝伐单抗（B）和T协同联合治疗。

2014年ASCO大会上的乳腺癌口头报告中，有一项AVATAXHER II期试验（EUDRACT 2009-013410-26）评估了T+多西他赛（D）新辅助治疗中添加贝伐单抗（B）是否能改善实现病理学完全缓解可能性较低的肿瘤（根据一个T + D疗程后FDG肿瘤摄取的相对变化[ΔSUV ]预测）的病理学完全缓解率。下面提前和大家分享这项研究。

研究方法

18岁以上，T2/3分期，N0/1 HER2+BC患者。患者接受两个T（8mg/kg，之后6mg/kg）+D （100mg/m²）疗程治疗（三周一个疗程）。1和2疗程间PET值≥ 70％ΔSUV的患者再接受4个疗程以上的T+D治疗，1个疗程的T治疗，之后进行手术（标准组）。那些ΔSUV<70％的患者按2:1的比例随机分配接受4疗程的T+D+B（15mg/kg;a组）或T+D（b组）治疗，之后都接受一个疗程的T治疗和手术治疗。主要终点指标是手术时的pCR率。对有关pCR率的ΔSUV阳性（PPV）和阴性预测值（NPV）以及安全性也进行了研究。

研究结果

26个试验点招募了152例患者（10例终止预治疗; ITT = 142）。标准组37/69（53.6％）的患者达到pCR，a组和b组分别为21/48（43.8％）及6/25（24.0％）。激素受体-ve / +ve患者的pCR率分别为：69.0％/42.5％（标准组），57.9％/34.5％（a组）和40.0％/13.3％（b组）。共有133例患者接受保守手术治疗。标准组保守手术患者占手术患者的84.8％，a组占 67.4％，b组占62.5％。未进行B治疗的患者中 ，一个疗程后的ΔSUV可预测pCR，PPV为52.9％，NPV为75％。毒性轻微，包括乏力，肌痛，流泪增加（所有患者≥ 1 AE）。3/4级AES（占31％的患者）包括中性粒细胞减少（8.6%），发热性中性粒细胞减少（3.6％），肌痛（3.6％），无力（2.9％），和指甲毒性（2.9％） 。

结论

T+D新辅助治疗中添加B治疗，可提高PET ΔSUV预测的pCR较低的肿瘤的pCR率，从24.0 ％至42.5％。通过选择低应答HER2阳性肿瘤，PET ΔSUV可能是优化HER2+BC患者新辅助治疗的一个有用工具。临床试验信息：2009-013410-26。

医脉通整理报道，转载请注明出处。

会议专题》》》2014年ASCO年会专题报道

阅读英文摘要

AVATAXHER: An open-label, randomized, multicenter study investigating the addition of bevacizumab (B) to neoadjuvant trastuzumab (T) plus docetaxel (D) in patients with early stage HER2-positive breast cancer (HER2+ BC) stratified according to PET change after one therapy cycle.（Abstract No:507）

Authors: Peter Andrew Kaufman, Gilles Freyer, Margaret Kemeny, et al.

Session Type: Oral Abstract Session

Background: T-based neoadjuvant chemotherapy achieves pCR rates of ~50% in HER2+ BC, enabling frequent conservative surgery. Pre-clinical and clinical data support the synergistic combination of B and T. The ph II AVATAXHER trial (EUDRACT 2009-013410-26) investigated whether adding B to neoadjuvant T+D improved pCR rates in tumors with a low likelihood of attaining pCR (predicted based on relative change in FDG tumoral uptake [ΔSUV] after one cycle of T+D).

Methods: Patients were ≥18 yrs old with stage T2/3, N0/1 HER2+ BC. Patients received two 3-weekly cycles of T (8 mg/kg, then 6 mg/kg) and D (100 mg/m2). Those with ≥70% ΔSUV in PET values between cycle 1 and 2 received four more cycles of T+D, one cycle of T, then surgery (standard arm). Those with <70% ΔSUV were randomized 2:1 to four cycles of T+D+B (15 mg/kg; arm a) or T+D (arm b), then one T cycle and surgery. The primary endpoint was pCR rate at surgery. The positive (PPV) and negative predictive value (NPV) of ΔSUV on pCR rate and safety were also investigated. 

Results: 152 patients were recruited at 26 sites (10 were withdrawn pretreatment; ITT=142). 37/69 (53.6%) patients in the standard arm achieved pCR, 21/48 (43.8%) in arm a and 6/25 (24.0%) in arm b. pCR rates in patients with hormone receptor –ve/+ve disease were: 69.0%/42.5% (standard arm), 57.9%/34.5% (arm a), and 40.0%/13.3% (arm b). Surgery (133 pts) was conservative in 84.8% of patients with surgery in the standard arm, 67.4% in arm a, and 62.5% in arm b. In patients without B, ΔSUV after one cycle predicted pCR with a PPV of 52.9% and a NPV of 75%. Toxicity was mild and included asthenia, myalgia, and increased lacrimation (all pts had ≥1 AE). Grade 3/4 AEs (in 31% of pts) included neutropenia (8.6% pts), febrile neutropenia (3.6%), myalgia (3.6%), asthenia (2.9%), and nail toxicity (2.9%). 

Conclusions: Adding B to neoadjuvant T+D, in tumors with a low likelihood of pCR predicted by PET ΔSUV, increased the pCR rate from 24.0% to 42.5%. PET ΔSUV, by selecting low responding HER2+ tumors, may be a useful tool for optimizing neoadjuvant therapy for HER2+ BC. Clinical trial information: 2009-013410-26.

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