The role of bevacizumab in targeted vascular endothelial growth factor therapy for epithelial ovarian cancer: an updated systematic review and meta-analysis

Figures & data

Table 1 Characteristics of included studies

Study	Diagnostic criteria	GOG/ECOG PS	Setting	n	Treating arm	Median age (range)
GOG-0218^Citation10,Citation11	GOG	GOG PS 0–2	First-line and maintenance	625 625 623	P + C + PL; PL maintenance P + C + Bev; PL maintenance P + C + Bev; Bev maintenance	60 (25–86) 60 (24–88) 60 (22–89)
ICON7^Citation12,Citation20	Local histopathological findings	ECOG PS 0–2	First-line and maintenance	764 764	P + C P + C + Bev; Bev maintenance	57 (18–81) 57 (24–82)
OCEANS^Citation14,Citation19	NR	ECOG PS 0–1	Recurrent, platinum-sensitive	242 242	G + C + P (combination and maintenance) G + C + Bev (combination and maintenance)	61 (28–86) 60 (38–87)
AURELIA^Citation13,Citation21	NR	ECOG PS 0–2	Recurrent, platinum-resistant	182 179	PAC or T or PLD PAC or T or PLD + Bev	61 (25–84) 61 (25–80)
GOG-0213^Citation3	NR	GOG PS 0–2	Recurrent, platinum-sensitive	374 374	P + C P + C + Bev; Bev maintenance	60

Abbreviations: P, paclitaxel; C, carboplatin; Bev, bevacizumab; G, gemcitabine; T, topotecan; PLD, pegylated liposomal doxorubicin; PAC, weekly paclitaxel; PL, placebo; GOG, Gynaecologic Oncology Group; ECOG, Eastern Cooperative Oncology Group; AUC, area under curve; PS, performance status; NR, not reported.

Figure 1 Flow diagram of the literature search and selection process.

Abbreviations: CNKI, Chinese Knowledge Infrastructure; CENTRAL, Cochrane Central Register of Controlled Trials; RCT, randomized controlled trial.

Figure 2 Risk of bias and quality assessment. (A) Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included studies. (B) Risk of bias summary: review authors’ judgments about each risk of bias item for each included study.

Figure 3 Forest plots of hazard ratios for progression-free survival (A and C) and overall survival (B and D). In patients with epithelial ovarian cancer treated with bevacizumab plus chemotherapy, compared with chemotherapy alone, as chemotherapy regimens of carboplatin plus paclitaxel or not (A and B). In patients with epithelial ovarian cancer with high risk of progression (FIGO stage IV disease or FIGO stage III disease and >1.0 cm of residual disease after debulking surgery) treated with bevacizumab plus chemotherapy, compared with chemotherapy alone, as chemotherapy regimens of carboplatin plus paclitaxel or not (C and D).

Abbreviations: CI, confidence interval; PC, paclitaxel and carboplatin; PFS, progression-free survival; OS, overall survival; bev, bevacizumab; con, control; FIGO, International Federation of Gynecology and Obstetrics; IV, inverse variance.

Figure 4 Funnel plots of hazard ratios for progression-free survival (A) and overall survival (B).

Abbreviations: PFS, progression-free survival; OS, overall survival; SE, standard error; PC, paclitaxel and carboplatin.

BurgerRASillMWMonkBJGreerBESoroskyJIPhase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group StudyJ Clin Oncol2007255165517118024863

 PubMed Web of Science ®Google Scholar

BurgerRABradyMFBookmanMAFlemingGFMonkBJHuangHIncorporation of bevacizumab in the primary treatment of ovarian cancerN Engl J Med20113652473248322204724

 PubMed Web of Science ®Google Scholar

PerrenTJSwartAMPfistererJA phase 3 trial of bevacizumab in ovarian cancerN Engl J Med20113652484249622204725

 PubMed Web of Science ®Google Scholar

OzaAMCookADPfistererJStandard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trialLancet Oncol20151692893626115797

 PubMed Web of Science ®Google Scholar

AghajanianCBlankSVGoffBAOCEANS: 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 cancerJ Clin Oncol2012302039204522529265

 PubMed Web of Science ®Google Scholar

AghajanianCGoffBNycumLRWangYVHusainABlankSVFinal overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancerGynecol Oncol2015139101626271155

 PubMed Web of Science ®Google Scholar

Pujade-LauraineEHilpertFWeberBBevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trialJ Clin Oncol2014321302130824637997

 PubMed Web of Science ®Google Scholar

PovedaAMSelleFHilpertFBevacizumab combined with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort of the randomized phase III AURELIA trialJ Clin Oncol2015333836383826282651

 PubMed Web of Science ®Google Scholar

ColemanRLBradyMFHerzogTJBevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trialLancet Oncol20171877979128438473

 PubMed Web of Science ®Google Scholar