Eric Pujade-Lauraine, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Paris; Béatrice Weber, GINECO and Centre Alexis Vautrin, Vandoeuvre-les-Nancy; Philippe Follana, GINECO and Centre Antoine-Lacassagne, Nice; Isabelle Ray-Coquard, GINECO and Centre Léon Bérard, Lyon, France; Felix Hilpert, Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Klinik für Gynäkologie und Geburtshilfe, Kiel; Alexander Reuss, AGO and Coordinating Center for Clinical Trials, Marburg; Pauline Wimberger, AGO and University of Duisburg-Essen, Essen, Germany; Andres Poveda, Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Instituto Valenciano de Oncologia, Valencia; Ana Oaknin, GEICO and Vall d'Hebron University Hospital, Barcelona, Spain; Gunnar Kristensen, Nordic Society of Gynaecological Oncology (NSGO) and Norwegian Radium Hospital, Oslo, Norway; Roberto Sorio, Multicenter Italian Trials in Ovarian Cancer and Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy; Ignace Vergote, Belgian Gynaecological Oncology Group and University Hospital Leuven, Leuven, Belgium; Petronella Witteveen, Dutch Gynecological Oncology Group and University Medical Center Utrecht, Utrecht, the Netherlands; Aristotelis Bamias, Hellenic Cooperative Oncology Group and University of Athens, Athens, Greece; Deolinda Pereira, GINECO and Instituto Português de Oncologia do Porto, Porto, Portugal; Mansoor Raza Mirza, NSGO and Rigshospitalet, Copenhagen, Denmark; and David Bollag, F. Hoffmann-La Roche, Basel, Switzerland.
J Clin Oncol. 2014 May 1;32(13):1302-8. doi: 10.1200/JCO.2013.51.4489. Epub 2014 Mar 17.
In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC.
Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.
The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients.
Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
在铂耐药性卵巢癌（OC）中，单药化疗是标准治疗。贝伐单抗单独使用以及与其他药物联合使用均具有活性。AURELIA 是我们所知的首个将贝伐单抗与铂耐药性 OC 中的化疗联合使用的随机 III 期试验。
符合条件的患者患有可测量/可评估的 OC，在完成基于铂的治疗后 <6 个月进展。患有难治性疾病、肠梗阻病史或 > 两种先前抗癌方案的患者不符合条件。在研究者选择化疗（聚乙二醇化脂质体多柔比星、每周紫杉醇或拓扑替康）后，患者被随机分配至单独使用化疗药物或联合贝伐单抗（每 2 周 10mg/kg 或每 3 周 15mg/kg），直至疾病进展、不可接受的毒性或同意退出。在单独使用化疗药物进展后，可交叉使用单药贝伐单抗。主要终点是根据 RECIST 评估的无进展生存期（PFS）。次要终点包括客观缓解率（ORR）、总生存期（OS）、安全性和患者报告的结果。
在 361 例患者中的 301 例发生 PFS 事件后，PFS 风险比（HR）为 0.48（95%CI，0.38 至 0.60；未分层对数秩 P<0.001）。单独化疗的中位 PFS 为 3.4 个月，而含贝伐单抗治疗的中位 PFS 为 6.7 个月。根据 RECIST，ORR 分别为 11.8%和 27.3%（P=0.001）。OS HR 为 0.85（95%CI，0.66 至 1.08；P<0.174；中位 OS 分别为 13.3 个月和 16.6 个月）。贝伐单抗治疗组更常见的是≥2 级高血压和蛋白尿。贝伐单抗治疗组有 2.2%的患者发生胃肠道穿孔。
与化疗相比，添加贝伐单抗可显著改善 PFS 和 ORR；OS 趋势不显著。未观察到新的安全性信号。
