2014年ASCO大会上的
紫杉醇+贝伐单抗联合治疗可以明显延长转移性乳腺癌患者的无进展生存期，但是存在不良反应，主要是神经病变和随时间逐渐加重的乏力。已经证实内分泌治疗+贝伐单抗方案的耐受性较好，或许可以作为紫杉醇+贝伐单抗一线治疗后的维持治疗方案。
研究方法
在这一前瞻性、随机、非盲III期试验中，经过紫杉醇+贝伐单抗一线治疗16-24周后未发生进展的、病理证实为ER+ HER2阴性的局部晚期或转移性乳腺癌患者，被随机分配到继续应用紫杉醇+贝伐单抗治疗组或内分泌治疗+贝伐单抗维持治疗组(依西美坦 25 mg/d+贝伐单抗15 mg/kg q3w)。主要试验终点是无进展生存期。我们预计紫杉醇+贝伐单抗组6个月无进展生存率由50%提高到65%，内分泌治疗+贝伐单抗维持治疗组6个月无进展生存率由50%提高到80%，共需要141例，计划有198位患者参与试验。计划在病例完成40%时进行中期分析。次要终点包括总生存率和毒性作用。
研究结果
截止到2013年5月，113位患者参与了试验，我们对其中98位完成了分析。患者年龄的中位数为55岁（范围35-86岁）。64%的患者应用内分泌治疗作为辅助治疗，24%的转移性乳腺癌患者应用内分泌治疗作为辅助治疗。随访时间的中位数为9.7个月（范围0.8-28.3个月）。紫杉醇+贝伐单抗组6个月无进展生存率为 70% (95% 置信区间(CI) 54,81.5) ，内分泌治疗+贝伐单抗维持治疗组6个月无进展生存率为54% (95% CI 38.5,67.2)(HR 1.2, 95% CI (0.7,1.9),p=0.56)。鉴于中期分析的结果，试验结束时无进展生存期的差异有显著性的可能性为7%。
紫杉醇+贝伐单抗组中11位患者死亡，内分泌治疗+贝伐单抗维持治疗组6位患者死亡。内分泌治疗+贝伐单抗维持治疗组3-4级不良反应的发生率更低(乏力：4% vs 14%；神经病变：0% vs 12%；疼痛：2% vs 8%；中性粒细胞减少：0% vs 12%)，严重不良反应的发生率也更低(13% vs 24%)。基于安全性和疗效的结果，IDMC决定立即停止入组，并按协议继续治疗。最后的分析将对随访的数据进行更新。
结论
没有达到预想的治疗效果，但是内分泌治疗+贝伐单抗维持治疗的安全性更高。我们计划进行探究性分析，找出哪一患者亚群可能会从中受益。临床试验信息: NCT01303679。
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
阅读摘要原文
Arobase: A phase III trial of exemestane (Exe) and bevacizumab (BEV) as maintenance therapy in patients (pts) with metastatic breast cancer (MBC) treated in first line with paclitaxel (P) and BEV—A Gineco study.（Abstract No:501）
Authors: Olivier Tredan, Philippe Follana, Isabelle Moullet, Claire Cropet, et al.
Session Type: Oral Abstract Session
Background: Combination of P+BEV significantly improves progression-free survival (PFS) in MBC pts, but is associated with adverse events (AEs), mainly neuropathy and fatigue worsening over time. Endocrine therapy (ET) combined to BEV has been proven tolerable and may be a option as maintenance therapy after P+BEV.
Methods: in this prospective, randomized, open label, phase III study, pts with histologically confirmed ER+ HER2- locally advanced or MBC, who had not progressed after 16-24 weeks of 1st-line P+BEV therapy, were randomized to P+BEV continuation vs ET+BEV (Exe 25 mg/d+BEV 15 mg/kg q3w). Primary endpoint was PFS. To demonstrate an improvement in the 6-month PFS rate (PFS-6m) from 50% with P+BEV to 65% with ET+BEV (2-sided α=5%) with 80% power, 141 events were requiered and 198 pts were planned. An interim analysis (IA) was planned after 40% of required events. Secondary endpoints included overall survival (OS) and toxicity.
Results: At the cut-off date for the IA (May 2013), 113 pts were included, 98 were analyzable. Median age was 55 (range 35-86). ET was given as adjuvant therapy in 64% of pts and in the metastatic setting in 24%. Median follow up was 9.7 months (range 0.8-28.3). PFS-6m was 70% (95% confidence interval (CI) 54, 81.5) with P+BEV and 54% (95% CI 38.5, 67.2) with ET+BEV (HR 1.2, 95% CI (0.7, 1.9), p=0.56). Given these interim results, the probability to show statistically significant PFS at the end of the study was 7%. Deaths were reported for 11 pts in the P+BEV arm vs 6 pts in the ET+BEV arm (median OS not reached). Grade 3-4 AEs rates were lower with ET+BEV (fatigue: 4% of pts vs 14%); neuropathy: 0% vs 12%; pain: 2% vs 8%; neutropenia: 0% vs 12%), as well as serious AEs related to treatment (13% vs 24%). Based on both safety and efficacy results, the IDMC decided to definitely stop the enrollment and to keep patients under tretment in the protocol.Follow-up data will be updated for the final analysis.
Conclusions: The efficacy hypothesis was not reached, despite a better safety profile of the ET+BEV maintenance therapy. Exploratory analyses are planned to identify potential subgroups benefiting from it. Clinical trial information: NCT01303679.
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