Adding bevacizumab to chemotherapy extended survival by about 4 months beyond the survival achieved with chemotherapy alone in chemotherapy-naïve patients with persistent, recurrent, or metastatic cervical cancer.
The findings seen at the interim analysis of the GOG(Gynecology Oncology Group) 240 study (Paclitaxel and Cisplatin or Topotecan With or Without Bevacizumab for Treating Patients With Stage IV-B, Recurrent, or Persistent Cervical Cancer) prompted the trial’s data safety monitoring committee to announce the study had reached its primary endpoint – a statistically significant increase in overall survival for patients given the regimen that included bevacizumab (Avastin). The interim analysis took place after 271 patients had died.
"The findings in this clinical trial are important because they are likely to change clinical practice and provide an opportunity to improve outcome in patients with recurrent cervical cancer who have previously had very limited treatment options," GOG study chair Dr. Krishnansu S. Tewari and also of University of California, Irvine Medical Center, Orange, said in a statement announcing the trial results.
The trial was designed to answer two questions: Whether topotecan in combination with paclitaxel was superior to cisplatin and paclitaxel in combination, and whether the addition of bevacizumab to either regimen improved overall survival.
The study comprised 452 patients in the United States and Spain with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment. The trial participants were randomized to four treatment arms: cisplatin 50 mg/m2 plus paclitaxel 135-175 mg/m2, with and without bevacizumab 15 mg/kg; and topotecan 0.75 mg/m2 d1-3 plus paclitaxel 175 mg/ m2 d1, with and without bevacizumab 15 mg/kg. The treatment cycles were repeated every 21 days until there was disease progression, unacceptable toxicity, or a complete response. In all, 225 received the bevacizumab-containing regimens and 227 received the standard regimens.
In an analysis conducted in 2012, it was determined that topotecan plus paclitaxel was not superior to the standard therapy of cisplatin plus paclitaxel and investigators, and patients were notified of the finding.
In the more recent analysis, those who received bevacizumab were 29% less likely to die than were those who did not get the drug – a significant difference (hazard ratio, 0.71). The median survival was 17 months vs. 13 months. The response rates were 48% for the bevacizumab regimens and 26% for the standard regimens.
Patients who received bevacizumab also experienced more grade 3 and 4 side effects, including bleeding (5% vs. 1%), thrombosis/embolism (9% vs. 2%), and gastrointestinal fistula (9% vs. 2%).
More than 12,000 women will be diagnosed with cervical cancer in the United States in 2013 and more than 4,000 women will die of the disease, according to estimates.
michele.sullivan@elsevier.com