Western Regional Blog – BC, YK, AB, NWT and Nunavut
TAKE-HOME MESSAGE This randomized trial enrolled 361 platinum-resistant ovarian cancer patients who received single-agent chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan) with or without bevacizumab. The addition of bevacizumab improved the response rate (27% vs 12%) and median PFS (6.7 vs 3.4 months). There was no statistically significant difference in median overall survival (16.6 vs 13.3 months), but this was confounded by the fact that 40% of the control arm patients crossed over to receive bevacizumab at the time of progression. The authors remarked that this study is the first to demonstrate a significant benefit in PFS for a combination regimen or biologic agent in patients with platinum-resistant ovarian cancer. Based on the results, the authors suggested that bevacizumab added to chemotherapy should be a standard treatment option. Richard Bambury, MD
PURPOSE In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC.
PATIENTS AND METHODS Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes.
RESULTS The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients.
CONCLUSION Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.
J. Clin. Oncol 2014 Mar 17;[EPub Ahead of Print], E Pujade-Lauraine, F Hilpert, B Weber, A Reuss, A Poveda, G Kristensen, R Sorio, I Vergote, P Witteveen, A Bamias, D Pereira, P Wimberger, A Oaknin, MR Mirza, P Follana, D Bollag, I Ray-Coquard