OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy With or Without Bevacizumab in Patients With Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
OCEANS: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Chemotherapy With or Without Bevacizumab in Patients With Platinum-Sensitive Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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DOI：
10.1200/jco.2012.42.0505
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发表时间：
2012-06-10
影响因子：
45.3
通讯作者：
Nycum, Lawrence R.
中科院分区：
文献类型：
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作者：
Aghajanian, Carol;Blank, Stephanie V.;Nycum, Lawrence R.
目的这项随机、多中心、盲法、安慰剂对照 III 期试验测试了贝伐珠单抗 (BV) 联合吉西他滨和卡铂 (GC) 与 GC 在铂敏感复发性卵巢癌、原发性腹膜癌或输卵管癌 (ROC) 中的疗效和安全性。 患者和方法铂敏感 ROC 患者 （一线铂类治疗后复发≥ 6 个月）和可测量疾病被随机分配至 GC 加 BV 或安慰剂 (PL) 组，为期 6 至 10 个周期。然后分别继续 BV 或 PL 直至疾病进展。主要终点是 RECIST 的无进展生存期 (PFS)；次要终点是客观缓解率、缓解持续时间 (DOR)、总生存期和安全性。结果 总体而言，484 名患者被随机分配。 BV 组的 PFS 优于 PL 组（风险比 [HR]，0.484；95% CI，0.388 至 0.605；对数秩 P < .0001）；中位 PFS 分别为 12.4 个月和 8.4 个月。添加 BV 后，客观缓解率（78.5% vs 57.4%；P < .0001）和 DOR（10.4 vs 7.4 个月；HR，0.534；95% CI，0.408 至 0.698）显着改善。没有发现新的安全问题。 BV 组中 3 级或以上高血压 (17.4% v < 1%) 和蛋白尿 (8.5% v < 1%) 发生频率更高。两组中性粒细胞减少症和发热性中性粒细胞减少症的发生率相似。 BV 组中的两名患者在停止研究治疗后出现胃肠道穿孔。 结论 在铂敏感 ROC 中，GC 加 BV，随后 BV 直至进展，与 GC 加 PL 相比，PFS 具有统计学意义的改善。
PurposeThis randomized, multicenter, blinded, placebo-controlled phase III trial tested the efficacy and safety of bevacizumab (BV) with gemcitabine and carboplatin (GC) compared with GC in platinum-sensitive recurrent ovarian, primary peritoneal, or fallopian tube cancer (ROC).Patients and MethodsPatients with platinum-sensitive ROC (recurrence >= 6 months after front-line platinum-based therapy) and measurable disease were randomly assigned to GC plus either BV or placebo (PL) for six to 10 cycles. BV or PL, respectively, was then continued until disease progression. The primary end point was progression-free survival (PFS) by RECIST; secondary end points were objective response rate, duration of response (DOR), overall survival, and safety.ResultsOverall, 484 patients were randomly assigned. PFS for the BV arm was superior to that for the PL arm (hazard ratio [HR], 0.484; 95% CI, 0.388 to 0.605; log-rank P < .0001); median PFS was 12.4 v 8.4 months, respectively. The objective response rate (78.5% v 57.4%; P < .0001) and DOR (10.4 v 7.4 months; HR, 0.534; 95% CI, 0.408 to 0.698) were significantly improved with the addition of BV. No new safety concerns were noted. Grade 3 or higher hypertension (17.4% v < 1%) and proteinuria (8.5% v < 1%) occurred more frequently in the BV arm. The rates of neutropenia and febrile neutropenia were similar in both arms. Two patients in the BV arm experienced GI perforation after study treatment discontinuation.ConclusionGC plus BV followed by BV until progression resulted in a statistically significant improvement in PFS compared with GC plus PL in platinum-sensitive ROC.