Improved Survival with Bevacizumab in Advanced Cervical Cancer (GOG240)

Disease site

Cervix

Publication month/year

February/2014

Study question

Evaluation the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.

Type of study

RCT: 2-by-2 factorial design.

Interventions compared
  •  Cisplatin and paclitaxel vs. Topotecan and paclitaxel.
  • Both regimens was studied with and without bevacizumab.
Experimental arm (Intervention)
  1. Control treatment + bevacizumab. (CT+B)
  2. Nonplatinum combination chemotherapy. (NP)
  3. Nonplatinum combination chemotherapy with bevacizumab. (NP+B)
Control arm

Cisplatin and paclitaxel. (CT)

Primary outcome
  • Overall survival
  • The frequency and severity of adverse events associated with each regimen.
Secondary outcome

Progression-free survival and response rate.

Inclusion criteria
  • Metastatic, persistent, or recurrent cervical carcinoma.
  • Adequate renal, hepatic, and bone marrow function.
  • Measurable disease.
Exclusion criteria
  • Being a candidate for curative therapy by means of pelvic exenteration.
  • Patients treated with chemotherapy for recurrence and those with nonhealing wounds, active bleeding, or inadequately anti coagulated for thromboembolism. 
Results
Chemotherapy-alone group Chemotherapy-plus-bevacizumab group
Randomised (n0) CT (114) / NP (111) CT + B (115) / NP + B (112)
Overall survival P=0.004 13.3 months 17 months
Response rate P=0.008 36% 48%
Hypertension Grade >=2 2% 25%
Thromboembolic events Grade >=3 1% 8%
Gastrointestinal fistulas 0% 3%
Conclusions
  • The addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival.
  • As compared with cisplatin–paclitaxel (either with or without bevacizumab) topotecan–paclitaxel was associated with a significantly higher risk of progression (hazard ratio, 1.39; 95% confidence interval [CI], 1.09 to 1.77) but it did not affect OS. 
Study limitations
  • Patients with advanced cervical cancer usually do not have a sustained response to chemotherapy and cannot receive multiple lines of chemotherapy because of unacceptable side effects.
  • Data are lacking on drugs that inhibit angiogenesis through non–VEGF-dependent pathway, as well as vascular disrupting agents.
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