尽管贝伐单抗已用于卵巢癌的治疗，但其最佳使用方法尚不清楚。为了研究贝伐单抗治疗结果随时间的变化，我们进行了一项队列研究，使用来自7项前瞻性随机III期临床试验的已发表数据（ICON7，GOG-0218，BOOST，GOG-0213，OCEANS，AURERIA和MITO16B），数据范围从2023年1月10日至1月31日。从ICON7试验的两个辅助分析中使用个体患者数据和肿瘤基因表达谱生成了一个由745例病例组成的ICON7-A队列。从其他研究中，已发表的Kaplan-Meier曲线进行了图形化分析。比较贝伐单抗治疗与安慰剂或无治疗的差异。比较贝伐单抗治疗组和对照组在给定时间点的限制均生存时间和相对进展风险。在ICON7-A队列（n = 745）中，限制均生存分析表明，在贝伐单抗停用之前（限制均生存时间比率为1.08，95％CI为1.05-1.11，P <0.001），贝伐单抗治疗组（n = 384）相较于对照组（n = 361）在无进展生存期（PFS）方面显著更好，而贝伐单抗停用后（0.79，95％CI为0.69-0.90，P <0.001），PFS显著更差，出现反弹效应。事后分析显示，无论在同源重组缺陷（HRD）亚型（在贝伐单抗停用之前，1.05，95％CI为1.02-1.09，P <0.001；停用后，0.79，95％CI为0.63-0.98，P =0.04） 还是非-HRD亚型（在贝伐单抗停用之前，1.08，95％CI为1.03-1.15，P <0.001；停用后，0.71，95％CI为0.56-0.90，P <0.001）的浆液亚型中，都观察到了类似的反弹现象，但在非浆液亚型（在贝伐单抗停用之前，1.11，95％CI为1.05-1.18，P <0.001；停用后，0.94，95％CI为0.78-1.15，P= 0.57）中未观察到。在基于Kaplan-Meier曲线的图像分析中，在整个ICON7和GOG-0218队列及其按预后因素、同源重组相关突变和化疗敏感性分层的亚组中一致观察到了反弹效应的趋势。相反，在GOG-0213、OCEANS、AURERIA和MITO16B的研究中未观察到这种趋势，这些研究中，经历复发的患者直到进展都接受了贝伐单抗治疗。在卵巢癌中，贝伐单抗在初始治疗后可能在大约1年内减少进展，但停用后可能增加随后的进展，而且不论HRD状态如何，这种情况在浆液亚型中都存在。结果表明，在一线治疗中，对于预后较短且不太可能出现反弹结果的患者，贝伐单抗可能更有益。

Although bevacizumab has been used in the treatment of ovarian cancer, its optimal use is unknown.To investigate time-dependent changes in the outcomes of bevacizumab therapy.This cohort study was conducted using published data from 7 previous randomized phase 3 clinical trials with bevacizumab (ICON7, GOG-0218, BOOST, GOG-0213, OCEANS, AURERIA, and MITO16B) from January 10 to January 31, 2023. From 2 ancillary analyses of the ICON7 trial with individual patient data and tumor gene expression profiles, an ICON7-A cohort was generated comprising 745 cases. From other studies, published Kaplan-Meier curves were graphically analyzed.Bevacizumab treatment vs placebo or no treatment.Restricted mean survival time and relative risk of progression at a given time point between bevacizumab treatment and control groups.In the ICON7-A cohort (n = 745), restricted mean survival analysis showed that bevacizumab treatment (n = 384) had significantly better progression-free survival (PFS) than the control (n = 361) before bevacizumab discontinuation (restricted mean survival time ratio, 1.08; 95% CI, 1.05-1.11; P < .001), but had significantly worse PFS after bevacizumab discontinuation (0.79; 95% CI, 0.69-0.90; P < .001), showing rebound. In a post hoc analysis, the rebound was similarly observed both in homologous recombination deficiency (HRD) (before, 1.05; 95% CI, 1.02-1.09; P < .001; after, 0.79; 95% CI, 0.63-0.98; P = .04) and non-HRD tumors (before, 1.08; 95% CI, 1.03-1.15; P < .001; after, 0.71; 95% CI, 0.56-0.90; P < .001) of the serous subtype, but not in the nonserous subtype (before, 1.11; 95% CI, 1.05-1.18; P < .001; after, 0.94; 95% CI, 0.78-1.15; P = .57). In Kaplan-Meier curve image-based analysis, the trend of rebound effect was consistently observed in the overall ICON7 and GOG-0218 cohorts and their subgroups stratified by prognostic factors, homologous recombination-associated mutations, and chemotherapy sensitivity. In contrast, no such trend was observed in the studies GOG-0213, OCEANS, AURERIA, and MITO16B, in which patients who experienced relapse received bevacizumab until progression.In ovarian cancer, bevacizumab may reduce progression for approximately 1 year after initiation, but discontinuation may increase subsequent progression in the serous subtype regardless of HRD status. The results suggest that in the first-line treatment, bevacizumab may be more beneficial in patients with a shorter prognosis who are less likely to experience the rebound outcome.