Pfisterer Jacobus, Joly Florence, Kristensen Gunnar, Rau Joern, Mahner Sven, Pautier Patricia, El-Balat Ahmed, Kurtz Jean-Emmanuel, Canzler Ulrich, Sehouli Jalid, Heubner Martin L, Hartkopf Andreas D, Baumann Klaus, Hasenburg Annette, Hanker Lars C, Belau Antje, Schmalfeldt Barbara, Denschlag Dominik, Park-Simon Tjoung-Won, Selle Frédéric, Jackisch Christian, Burges Alexander, Lück Hans-Joachim, Emons Günter, Meier Werner, Gropp-Meier Martina, Schröder Willibald, de Gregorio Nikolaus, Hilpert Felix, Harter Philipp
Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group and Gynecologic Oncology Center, Kiel, Germany.
Groupe d'Investigateurs National des Etudes des Cancers Ovariens et du sein (GINECO) and Centre François Baclesse, University Caen Normandie, Caen, France.
J Clin Oncol. 2023 Feb 1;41(4):893-902. doi: 10.1200/JCO.22.01010. Epub 2022 Nov 4.
To compare standard versus extended duration of bevacizumab treatment in combination with front-line chemotherapy in women with newly diagnosed stage IIB-IV ovarian cancer.
In this multicenter, open-label, randomized phase III trial (ClinicalTrials.gov identifier: NCT01462890), patients with newly diagnosed International Federation of Gynecology and Obstetrics stage IIB-IV epithelial ovarian, fallopian tube, or peritoneal cancer underwent primary cytoreductive surgery followed by six cycles of chemotherapy (paclitaxel 175 mg/m plus carboplatin area under the curve 5 once every 3 weeks) and bevacizumab (15 mg/kg once every 3 weeks). Patients were randomly assigned 1:1 to receive bevacizumab for either 15 or 30 months, stratified by International Federation of Gynecology and Obstetrics stage/residual tumor. The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST version 1.1. Secondary end points included overall survival (OS), safety, and tolerability.
Between November 11, 2011, and August 6, 2013, 927 women were randomly assigned. There was no difference in PFS between treatment arms (hazard ratio, 0.99; 95% CI, 0.85 to 1.15; unstratified log-rank = .90). Median PFS was 24.2 versus 26.0 months with standard versus extended duration of bevacizumab, respectively; restricted mean PFS was 39.5 versus 39.3 months, respectively. There was no OS difference between treatment arms (hazard ratio, 1.04; 95% CI, 0.87 to 1.23; = .68). Serious/nonserious adverse events of special interest occurred in 29% versus 34% of patients in the standard versus experimental arms, respectively, and were consistent with the known safety profile of standard bevacizumab.
Longer treatment duration with bevacizumab for up to 30 months did not improve PFS or OS in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer. A bevacizumab treatment duration of 15 months remains the standard of care.
比较贝伐单抗联合一线化疗治疗新诊断的IIB-IV期卵巢癌女性患者时标准疗程与延长疗程的疗效。
在这项多中心、开放标签、随机III期试验（ClinicalTrials.gov标识符：NCT01462890）中，新诊断为国际妇产科联盟（FIGO）IIB-IV期上皮性卵巢癌、输卵管癌或腹膜癌的患者接受了初次肿瘤细胞减灭术，随后进行六个周期的化疗（紫杉醇175mg/m²加卡铂曲线下面积5，每3周一次）和贝伐单抗（15mg/kg，每3周一次）。患者按1:1随机分组，接受贝伐单抗治疗15个月或30个月，按FIGO分期/残留肿瘤进行分层。主要终点是根据RECIST 1.1版由研究者评估的无进展生存期（PFS）。次要终点包括总生存期（OS）、安全性和耐受性。
在2011年11月11日至2013年8月6日期间，927名女性被随机分组。各治疗组之间的PFS无差异（风险比，0.99；95%CI，0.85至1.15；未分层对数秩检验P = 0.90）。贝伐单抗标准疗程与延长疗程的中位PFS分别为24.2个月和26.0个月；受限平均PFS分别为39.5个月和39.3个月。各治疗组之间的OS无差异（风险比，1.04；95%CI，0.87至1.23；P = 0.68）。标准治疗组与试验组分别有29%和34%的患者发生了特别关注的严重/非严重不良事件，且与标准贝伐单抗已知的安全性特征一致。
对于原发性上皮性卵巢癌、输卵管癌或腹膜癌患者，将贝伐单抗治疗时间延长至30个月并未改善PFS或OS。15个月的贝伐单抗治疗疗程仍是标准治疗方案。
