Ovarian cancer (OC) is the eighth leading cause of cancer death among women worldwide. Over two-thirds of patients are diagnosed at an advanced stage, which carries a high risk of recurrence and low five-year survival rates ^[1–3]. Angiogenesis is a critical pathway for tumour growth and metastasis. Bevacizumab, the first monoclonal antibody to target vascular endothelial growth factor (VEGF), is a core targeted therapy in the treatment of advanced ovarian cancer (AOC) ^[4]. This study conducted a systematic review of the efficacy and safety data of bevacizumab in first-line, maintenance and recurrence treatments, with the aim of clarifying its clinical value in different risk groups and treatment lines. This provides evidence for precision medicine ^[5].

● First-line treatment setting: 

Based on the results of the GOG-0218 and ICON-7 phase III trials, the standard regimen for newly diagnosed advanced ovarian cancer is maintenance bevacizumab therapy following platinum-based chemotherapy ^[6-9]. The real-world RESPONSE study further confirmed that maintenance therapy significantly improves overall patient survival (HR=0.62, 95% CI=0.42–0.91, p=0.01) ^[10]. However, the BOOST trial indicated that extending the duration of treatment beyond 30 months did not provide any additional benefit, and that 15 months was the optimal duration ^[11].

● Recurrent treatment setting:

Bevacizumab has been shown to be effective in treating both platinum-sensitive and platinum-resistant recurrent cases. In the AURELIA Phase III trial, median progression-free survival (PFS) for platinum-resistant patients receiving combination chemotherapy increased from 3.4 months to 6.7 months (hazard ratio (HR)=0.48, 95% confidence interval (CI)=0.38-0.60, p<0.001), and crossover use after disease progression reduced the risk of death further ^[12,13]. In platinum-sensitive patients, the GOG-0213 trial demonstrated median PFS of 13.8 months with combination chemotherapy plus maintenance therapy (HR=0.63, p<0.0001) [20], and the OCEANS trial confirmed that maintenance therapy significantly prolonged PFS (12.4 months vs. 8.4 months, HR=0.48, p<0.0001) ^[14,15]. 

● Re-challenge setting:

Bevacizumab remains effective when re-administered after disease progression. In the JGOG3023 Phase II trial, the median PFS for recurrent platinum-resistant patients receiving re-challenge therapy increased from 3.1 months to 4.0 months (HR = 0.54, 95% CI = 0.32–0.90, p = 0.0082). The MITO16b/MANGO-OV2/ENGOT-ov17 phase III trial demonstrated a median progression-free survival (PFS) of 11.8 months in patients with platinum-sensitive recurrent disease who received rechallenge therapy (hazard ratio [HR] = 0.51, p < 0.0001) ^[16]. Combination with PARP inhibitors: The PAOLA-1 Phase III trial confirmed the significant efficacy of bevacizumab plus olaparib in patients with homologous recombination deficiency (HRD), with a median PFS of 46.8 months (HR = 0.41, 95% CI = 0.32–0.54), including a median PFS of 60.7 months in patients with a BRCA mutation ^{[5, 17]}. This combination has been approved as a first-line maintenance therapy for HRD-positive advanced ovarian cancer ^[18,19]. The OVARIO Phase II trial demonstrated a median PFS of 28.3 months for bevacizumab plus niraparib in HRD-positive patients ^[20].

● Risk Stratification Breakthrough: 

While it was previously thought that bevacizumab only benefited high-risk patients, a post-hoc analysis of the PAOLA-1 trial revealed that low-risk patients (stage III with complete resection) who received olaparib maintenance therapy achieved a five-year progression-free survival rate of 72%. This was significantly higher than the 28% achieved by the bevacizumab monotherapy group ^[21]. Furthermore, the ICON-7 trial's imaging analysis demonstrated that the efficacy of bevacizumab is unaffected by risk stratification ^[22].

● Biomarker guidance: 

HRD status is a core prognostic indicator. Patients with HRD demonstrate a significant benefit, whereas those without HRD show no clear advantage (HR = 1.01, 95% CI = 0.77–1.33) ^[17]. The KELIM score (based on CA-125 clearance rate) is used to assess chemotherapy sensitivity. Patients at high risk with a score of less than 1.0 (chemotherapy-insensitive) demonstrate greater overall survival (OS) benefit with bevacizumab ^{[23, 24]}.

The safety profile of bevacizumab is based on data from over 5,700 patients with malignant tumours, which demonstrates generally good tolerability ^[25]. Common adverse reactions include hypertension, fatigue, diarrhoea and abdominal pain, predominantly grades 1–2 ^[6,12,26]. The incidence of hypertension and proteinuria is lower when bevacizumab is combined with olaparib than with bevacizumab monotherapy ^{[5, 27]}. Serious adverse reactions are uncommon, with gastrointestinal perforation occurring in 3% of patients during first-line treatment and less than 2% during recurrent treatment ^[6,26]. Risk factors include a history of diverticulitis and abdominal abscesses ^[28]. Elderly patients (aged ≥70 years) exhibit a slightly higher incidence of hypertension, but their overall toxicity profiles show no significant difference compared to those of younger patients ^[29,30]. （For a summary of the experiments, see the table below）

Bevacizumab has been shown to provide significant benefits throughout the entire treatment cycle of advanced ovarian cancer, including first-line maintenance therapy, treatment for recurrence, and re-challenge therapy. It is particularly valuable for HRD-positive patients. Contrary to the previous limitation that it only benefits high-risk patients, HRD-positive low-risk patients can also achieve long-term survival benefits from bevacizumab combined with PARP inhibitors, with a remarkable 5-year progression-free survival rate ^[21]. Bevacizumab has a favourable safety profile, with preventable and manageable adverse reactions. Its safety profile is further enhanced when combined with PARP inhibitors, making it suitable for long-term maintenance therapy.

● Treatment Decision Optimisation: 

For HRD-positive patients, the preferred recommendation is bevacizumab combined with olaparib maintenance therapy. In the absence of clear biomarkers, both low- and high-risk patients may be considered for treatment. High-risk patients scoring <1.0 on the KELIM score demonstrate greater benefit ^[23,24]. Timing of therapy: Prioritise bevacizumab in first-line treatment to maximise survival benefit; re-challenge therapy may be considered after disease progression ^[31,32]. Safety Management: Assess risk factors such as gastrointestinal perforation and cardiovascular disease prior to administration. Blood pressure and urine protein should be regularly monitored during treatment; patients with hypertension must achieve blood pressure control before therapy is initiated ^[25,33].