Studies reported by the University of California, Tewari et al. Showed that with the extension of follow-up time, the overall survival curves of patients in the chemotherapy combined with bevacizumab group and the chemotherapy alone group remained separated, and there was no disease progression after bevacizumab treatment. “Rebound effect” (that is, the survival period after stopping bevacizumab is shorter than that after stopping chemotherapy alone). This finding conceptually validated the effectiveness and tolerability of bevacizumab in advanced cervical cancer. (Lancet. Online version July 27, 2017). This study is a randomized controlled, open-label phase III clinical trial (GOG-240). The researchers enrolled patients with metastatic, persistent, or recurrent cervical cancer from 81 centers in the United States, Canada, and Spain. Patients were randomly divided into four groups: cisplatin (50 mg / m2, d1 or d2), paclitaxel (135 mg / m2 or 175 mg / m2, d1) with / without bevacizumab (15 mg, d1) Two groups, cisplatin, paclitaxel (175 mg / m2, d1), topotecan (0.75 mg / m2, d1 ~ 3) with or without bevacizumab. Treatment until disease progression occurs, intolerable adverse reactions occur, the patient voluntarily withdraws from the study or achieves complete remission, or the patient ends medication.
The primary endpoints of the study were overall survival (OS) and adverse events. The blinded data and safety committee conducted a second interim analysis and final analysis. From April 6, 2009 to January 3, 2012, a total of 452 patients were enrolled in the study (225 patients were treated with two separate chemotherapy regimens, and 227 patients were added bevacizumab on the basis of the two chemotherapy regimens). As of March 7, 2014, a total of 348 deaths have reached the predetermined final analysis threshold.
Compared with the chemotherapy alone group, the overall survival of patients in the chemotherapy plus bevacizumab group was significantly improved: the median OS of the chemotherapy plus bevacizumab group was 16.8 months, and the chemotherapy alone group was 13.3 months (HR = 0.77, 95% CI 0.62 ~ 0.95; P = 0.007). Among patients who did not receive prior pelvic radiation therapy, the median OS of the chemotherapy combined with bevacizumab group and the chemotherapy alone group was 24.5 months and 16.8 months (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 of the chemotherapy plus bevacizumab group was 8.4 months, and the chemotherapy group was 7.1 months (HR = 0.83, 95% CI 0.66 ~ 1.05 ; P = 0.06). Of the 220 patients in the chemotherapy plus bevacizumab group, 32 (15%) had fistulas, and only 3 (1%) in the chemotherapy alone group. There were 13 cases (6%) and 1 case (<1%) of grade 3 fistula occurred in the two groups. There were no fistula events that led to emergency surgery, sepsis, or death.