Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer

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 Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial 
  
To the Editor:

In a previous issue of Journal of Clinical Oncology, we reported results from the open-label, randomized phase III AURELIA (Avastin Use in Platinum-Resistant Epithelial Ovarian Cancer) trial demonstrating that combining bevacizumab with single-agent chemotherapy for treatment of platinum-resistant recurrent ovarian cancer (PROC) significantly improved progression-free survival (PFS), the primary end point, as well as the objective response rate (ORR) and the patient-reported outcome end point of abdominal/GI symptoms in the intent-to-treat population of 361 patients.^1,2 We observed no significant difference in overall survival (OS) between treatment arms, though the trial was not designed for us to formally compare OS. In addition, the extensive cross-over of 40% of patients to bevacizumab from chemotherapy alone complicated interpretation...... 

.... The main limitation of these exploratory analyses is that assessing individual chemotherapy partners for bevacizumab was not an objective of AURELIA. However, exploring consistency of effect in clinical trials is important, not necessarily for guiding treatment practice, but at least for hypothesis generation, particularly if a plausible biologic explanation for differences exists. Although consistency, on the basis of treatment effect estimates and 95% CIs, was seen between cohorts, the effect on PFS, ORR, and OS of combining bevacizumab with weekly paclitaxel was remarkable. These hypothesis-generating observations should be considered when investigators design new trials in PROC.