一项转移性乳腺癌一线紫杉类药物联合贝伐珠单抗治疗后接受依西美坦加贝伐珠单抗维持治疗的 III 期临床试验：GINECO 研究。
A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study.
机构信息
Department of Medical Oncology, Centre Léon Bérard, Lyon; CNRS UMR5286, Cancer Research Center of Lyon, Lyon.
Department of Medical Oncology, Centre Antoine Lacassagne, Nice.
出版信息
Ann Oncol. 2016 Jun;27(6):1020-1029. doi: 10.1093/annonc/mdw077. Epub 2016 Feb 24.
BACKGROUND
Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC.
PATIENTS AND METHODS
In this prospective, open-label, phase III study, patients with histologically confirmed ER-positive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events.
RESULTS
The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5-66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively.
CONCLUSION
In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV.
CLINICALTRIALSGOV
NCT01303679.
背景
转移性乳腺癌（MBC）一线化疗后，除了缓解或肿瘤稳定外，维持治疗策略尚未得到广泛研究。内分泌治疗联合贝伐珠单抗可能是雌激素受体（ER）阳性 MBC 的一个有用选择。
患者和方法
在这项前瞻性、开放标签、III 期研究中，经组织学证实为 ER 阳性、HER2 阴性 MBC 且在接受紫杉醇加贝伐珠单抗（T + BEV）治疗 16-24 周后疾病无进展的患者被随机分为继续 T + BEV 或维持贝伐珠单抗加依西美坦（E + BEV）。主要终点是从随机分组到无进展生存期（PFS）的无进展生存期（PFS）。为了有 80%的把握检测到 6 个月无进展生存率（PFS6m）从 50%提高到 65%，需要 186 名可评估患者总共发生 141 例 PFS 事件。计划在需要的事件达到 40%后进行中期分析。
结果
在 98 名患者的中期分析中，研究结束时达到 PFS 统计学显著改善的概率仅为 7%。这导致独立数据和监测委员会建议终止患者入组。在所有随机患者（总共 117 名）中位随访 21 个月后，从随机分组开始的 PFS6m 为 T + BEV 组的 67.2%（95%置信区间[CI] 53.6-77.7）和 E + BEV 组的 55.2%（95%CI 41.5-66.9）[风险比（HR）：1.0，95%CI 0.7-1.5，P = 0.998]。T + BEV 和 E + BEV 组中，从 BEV 开始的中位 PFS 分别为 12.5 和 12.3 个月。在 T + BEV 组中，大多数患者（94.9%）因毒性（49.2%）过早停止使用紫杉醇。中位随访 35 个月后更新的数据显示，T + BEV 和 E + BEV 组的死亡率分别为 44%和 55%。
结论
在这项试验中，一线 T + BEV 后无疾病进展的 ER 阳性、HER2 阴性 MBC 患者接受 E + BEV 维持治疗并未获得比继续 T + BEV 更长的 PFS。
临床试验.gov：NCT01303679。
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