Bevacizumab Significantly Improves Progression-Free Survival in Patients With Epithelial Ovarian Cancer

Progression-free survival (PFS) in patients with epithelial ovarian cancer (EOC) was significantly improved by adding bevacizumab to the combination therapy of carboplatin and paclitaxel, but it did not make a significant difference in overall survival (OS), according to a study published in Pharmaceuticals.¹

Over 95% of ovarian cancer cases are EOC, which encompasses 5 distinct histotypes. Although early-stage ovarian cancer is highly curable, the researchers noted that it mainly presents itself in stages III or IV; late-stage ovarian cancer mortality is over 75%.

One of the primary first-line ovarian cancer treatments is the combination therapy of carboplatin and paclitaxel, which is often further combined with bevacizumab.² The FDA approved bevacizumab in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab, in June 2018 for patients with stage III or IV ovarian cancer after initial surgical resection.¹

Therefore, the NCCN guideline recommends paclitaxel/carboplatin/bevacizumab plus maintenance bevacizumab therapy as the preferred primary care regimen for stages II, III, and IV ovarian cancer.² However, the survival benefit of adding bevacizumab to this combination therapy remains controversial since no OS benefit was found in previous clinical trials.³

Although it is anticipated to reduce ovarian cancer recurrence, the researchers noted that bevacizumab’s overall safety profile and survival benefit need further evaluation.¹ Consequently, they conducted a systematic review to evaluate the efficacy and safety of incorporating bevacizumab into the combination therapy of carboplatin and paclitaxel for treating patients with EOC.

Adding bevacizumab to the combination therapy of carboplatin and paclitaxel significantly improved progression-free survival (PFS) in patients with epithelial ovarian cancer (EOC). | Image Credit: LASZLO - stock.adobe.com

To conduct their review, the researchers searched various online databases, like PubMed and Embase, through February 2024 for randomized controlled trials (RCTs) that compared carboplatin and paclitaxel with and without bevacizumab in patients with ovarian cancer.

Two independent reviewers screened the titles and abstracts of all identified studies to verify their eligibility; disagreements were resolved through discussion with a third reviewer. They also manually searched the references of eligible studies to identify any additional sources.

The researchers extracted various data from each eligible study, including study characteristics, population, interventions, and outcomes. The efficacy outcomes analyzed included OS and PFS. Additionally, the researchers determined the safety outcomes based on 16 adverse events, like hypertension, anemia, and pain.

The primary literature search yielded 490 studies, but the researchers used 7 for their analysis. The 7 studies included 5110 patients, spanning numerous countries, including the US, Canada, and the United Kingdom.

The researchers found that OS did not significantly differ between patients with EOC who received combination therapy with bevacizumab and those who did not receive bevacizumab, which they considered the control group (HR, 0.95; 95% CI, 0.87-1.03; P = .19). Conversely, compared to the control group, patients who received combination therapy with bevacizumab experienced significantly improved PFS (HR, 0.73; 95% CI, 0.58-0.92; P = .008).

As for safety outcomes, receiving combination therapy with bevacizumab was associated with a significantly higher incidence of hypertension (relative risk [RR], 5.36; 95% CI, 2.94-9.76; P < .00001), non-central nervous system (CNS) bleeding (RR, 3.63; 95% CI, 2.65-4.99; P < .00001), and pain (RR, 1.12; 95% CI, 1.05-1.20; P = .001) compared with the control group. This group was also associated with a significantly higher incidence of proteinuria (RR, 4.31; 95% CI, 1.09-17.00; P = .04), gastrointestinal (GI) perforation (RR, 3.93; 95% CI, 1.31-11.79; P = .01), and any thromboembolic events (RR, 1.81; 95% CI, 1.28-2.57; P = .0008) than the control group.

However, between the 2 groups, there was no significant difference in the incidence of heart failure, neutropenia, CNS bleeding, anemia, febrile neutropenia, GI disorders, wound complications, and dermatologic disorders.

The researchers acknowledged their limitations, including that they had little data on heart failure, anemia, thromboembolic events, febrile neutropenia, and dermatologic events; this was because of an inadequate number of eligible clinical trials. Despite their limitations, they made treatment suggestions based on their findings.

“...careful monitoring and supportive care should be facilitated to avoid underestimation and inadequate treatment of potential overlapping adverse events in concomitant use of cytotoxic and antiangiogenic agents as part of efforts to maintain the quality of life in patients with ovarian cancer,” the authors concluded.

References

1. Kim YJ, Lee HM, Lee GE, Yoo JH, Lee HJ, Rhie SJ. Optimizing outcomes: bevacizumab with carboplatin and paclitaxel in 5110 ovarian cancer patients-asystematic review and meta-analysis. Pharmaceuticals (Basel). 2024;17(8):1095. doi:10.3390/ph17081095
2. Ovarian cancer. NCCN Guidelines for Patients. Accessed September 10, 2024. https://www.nccn.org/patientresources/patient-resources/guidelines-for-patients/guidelines-for-patients-details?patientGuidelineId=32
3. Colomban O, Tod M, Peron J, et al. Bevacizumab for newly diagnosed ovarian cancers: best candidates among high-risk disease patients (ICON-7). JNCI Cancer Spectr. 2020;4(3):pkaa026. doi:10.1093/jncics/pkaa026