Advanced cervical cancer chemotherapy combined with bevacizumab has certain advantages

A study reported by Tewari et al. from the University of California, published in the online version of The Lancet on July 27, 2017, showed that with extended follow-up time, the overall survival curves of patients in the chemotherapy combined with bevacizumab group and the chemotherapy alone group remained separated, with no "rebound effect" observed after bevacizumab treatment — meaning the survival period after stopping bevacizumab was not shorter than after stopping chemotherapy alone. This finding conceptually validated both the effectiveness and tolerability of bevacizumab in advanced cervical cancer.

The study was a randomized controlled, open-label phase III clinical trial (GOG-240). Researchers enrolled patients with metastatic, persistent, or recurrent cervical cancer from 81 centers across the United States, Canada, and Spain. Patients were randomly divided into four groups: cisplatin (50 mg/m², d1 or d2) plus paclitaxel (135 mg/m² or 175 mg/m², d1) with or without bevacizumab (15 mg/kg, d1); and cisplatin plus paclitaxel (175 mg/m², d1) plus topotecan (0.75 mg/m², d1–3) with or without bevacizumab. Treatment continued until disease progression, intolerable adverse reactions, voluntary patient withdrawal, complete remission, or patient decision to stop medication.

The primary endpoints of the study were overall survival (OS) and adverse events. A blinded data and safety committee conducted a second interim analysis and a final analysis. From April 6, 2009 to January 3, 2012, a total of 452 patients were enrolled — 225 receiving two separate chemotherapy regimens alone, and 227 receiving bevacizumab added to those regimens. As of March 7, 2014, a total of 348 deaths had been reached, meeting the predetermined final analysis threshold.

Compared with the chemotherapy alone group, overall survival in the chemotherapy plus bevacizumab group was significantly improved. The median OS of the bevacizumab group was 16.8 months versus 13.3 months in the chemotherapy alone group (HR = 0.77, 95% CI 0.62–0.95; P = 0.007). Among patients who had not received prior pelvic radiation therapy, the benefit was even more pronounced — median OS was 24.5 months in the bevacizumab group compared to 16.8 months in the chemotherapy alone group (HR = 0.64, 95% CI 0.37–1.10; P = 0.11).

However, the difference in OS after tumor progression between the two groups was not statistically significant. The median OS after progression in the bevacizumab group was 8.4 months versus 7.1 months in the chemotherapy alone group (HR = 0.83, 95% CI 0.66–1.05; P = 0.06).

In terms of safety, fistulas were the most notable adverse event of concern. Of the 220 patients in the chemotherapy plus bevacizumab group, 32 (15%) developed fistulas, compared to only 3 (1%) in the chemotherapy alone group. Grade 3 fistulas occurred in 13 cases (6%) in the bevacizumab group and 1 case (less than 1%) in the chemotherapy alone group. Importantly, there were no fistula events that led to emergency surgery, sepsis, or death, suggesting that while the risk of fistula is meaningfully elevated with bevacizumab, it remains manageable within a monitored clinical setting.