晚期卵巢癌精准治疗的核心靶向选择——贝伐珠单抗
发布日期：
2026-01-07
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卵巢癌(OC)是全球女性第八大致死性癌症，超三分之二患者确诊时已处于晚期，复发风险高且5年生存率低[1-3]。血管生成是肿瘤生长和转移的关键环节，贝伐珠单抗作为首个靶向血管内皮生长因子(VEGF)的单克隆抗体，是晚期卵巢癌(AOC)治疗领域的核心靶向药物[4]。该研究通过系统梳理贝伐珠单抗在一线、维持及复发治疗中的疗效与安全性数据，明确其在不同风险人群和治疗线中的临床价值，为精准治疗提供依据[5]。



贝伐珠单抗


结果与数据支撑


DIAGREAT

不同治疗场景的疗效表现



01


● 一线治疗场景：基于GOG-0218和ICON-7两项III期试验结果，贝伐珠单抗联合铂类化疗后继续贝伐珠单抗维持治疗成为新诊断晚期卵巢癌的标准方案[6-9]。真实世界RESPONSE研究进一步证实，维持治疗可显著改善患者OS(HR=0.62，95% CI=0.42-0.91，p=0.01)[10]。但BOOST试验表明，治疗时长延长至30个月并未带来额外获益，15个月为最优疗程 [11]。


● 复发治疗场景：贝伐珠单抗对铂敏感和铂耐药复发患者均有效。AURELIA III期试验中，铂耐药患者联合化疗后中位 PFS从3.4个月提升至6.7个月(HR=0.48，95% CI=0.38-0.60，p<0.001)，且疾病进展后交叉使用仍能降低死亡风险[12,13]；铂敏感患者中，GOG-0213试验显示联合化疗+维持治疗的中位PFS达13.8个月(HR=0.63，p<0.0001)[20]，OCEANS试验也证实维持治疗可显著延长PFS(12.4个月vs.8.4个月，HR=0.48，p<0.0001)[14,15]。 


● 再挑战治疗场景：疾病进展后再次使用贝伐珠单抗仍具疗效。JGOG3023 II期试验中，铂耐药复发患者再挑战治疗的中位PFS从 3.1个月提升至4.0个月(HR=0.54，95%CI=0.32-0.90，p=0.0082)[2]；MITO16b/MANGO-OV2/ENGOT-ov17 III期试验显示，铂敏感复发患者再挑战治疗的中位PFS达11.8个月(HR=0.51，p<0.0001)[16]。 联合PARP抑制剂场景：PAOLA-1 III期试验证实，贝伐珠单抗联合奥拉帕利对同源重组缺陷(HRD)阳性患者疗效显著，中位 PFS达46.8个月(HR=0.41，95% CI=0.32-0.54)，其中BRCA 突变患者中位PFS高达60.7个月[5,17]。该组合已获批作为HRD阳性晚期卵巢癌的一线维持治疗方案[18,19]。OVARIO II期试验显示，贝伐珠单抗联合尼拉帕利对HRD阳性患者的中位PFS达28.3个月[20]。

晚期卵巢癌精准治疗的核心靶向选择——贝伐珠单抗

晚期卵巢癌精准治疗的核心靶向选择——贝伐珠单抗



DIAGREAT

适用人群的风险分层与生物标志物



02


● 风险分层突破：传统观点认为贝伐珠单抗仅对高危患者有益，但 PAOLA-1试验事后分析显示，低危患者(III 期完全切除)联合奥拉帕利维持治疗的5年无进展生存率达72%，显著高于单用贝伐珠单抗组(28%)[21]。ICON-7试验影像学分析也表明，贝伐珠单抗的疗效不受风险分层影响[22]。 


● 生物标志物指导：HRD状态是核心预测指标，HRD阳性患者获益显著，而HRD阴性患者无明显获益(HR=1.01，95% CI=0.77-1.33)[17]。KELIM评分(基于CA-125消除速率)可评估化疗敏感性，评分< 1.0(化疗不敏感)的高危患者使用贝伐珠单抗后OS获益更显著[23,24]。 



DIAGREAT

安全性与耐受性



03


贝伐珠单抗的安全性基于5700余例恶性肿瘤患者数据，总体耐受性良好[25]。常见不良反应为高血压、疲劳、腹泻和腹痛，多为1-2级[6,12,26]。与奥拉帕利联合使用时，高血压和蛋白尿发生率低于单用贝伐珠单抗[5,27]。 严重不良反应发生率较低，胃肠道穿孔在一线治疗中发生率为3%，复发治疗中<2%[6,26]，其风险因素包括憩室炎病史、腹腔脓肿等[28]。老年患者(≥70 岁)高血压发生率略高，但总体毒性与年轻患者无显著差异[29,30]。(实验汇总见下表)



贝伐珠单抗


研究结论与临床启示


DIAGREAT

核心结论



01


贝伐珠单抗贯穿晚期卵巢癌全治疗周期，一线维持治疗、复发治疗及再挑战治疗均能带来显著获益，尤其对HRD阳性患者价值突出。 打破 “仅高危患者获益” 的局限，HRD阳性的低危患者也能从贝伐珠单抗联合PARP抑制剂治疗中获得长期生存benefit，5年无进展生存率可观[21]。 贝伐珠单抗安全性良好，不良反应可防可控，联合PARP抑制剂时安全性更优，适合长期维持治疗[5]。



DIAGREAT

临床启示



02


● 治疗决策优化：HRD阳性患者优先推荐贝伐珠单抗联合奥拉帕利维持治疗；无明确生物标志物时，低危和高危患者均可考虑使用，KELIM评分<1.0 的高危患者获益更显著[23,24]。治疗时机选择：优先在一线治疗中使用贝伐珠单抗，可最大化生存获益，疾病进展后可考虑再挑战治疗[31,32]。 安全性管理：用药前需评估胃肠道穿孔、心血管疾病等风险因素，用药期间定期监测血压和尿蛋白，高血压患者需控制血压后再用药[25,33]。   



文献参考：


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DIAGREAT

药物浓度监测全自动化学发光解决方案

甲氨蝶呤早期药物监测与急性肾损伤的相关性

甲氨蝶呤早期药物监测与急性肾损伤的相关性

甲氨蝶呤早期药物监测与急性肾损伤的相关性

甲氨蝶呤早期药物监测与急性肾损伤的相关性


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