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Bevacizumab, chemotherapy combination extended PFS in platinum-resistant ovarian cancer
The addition of bevacizumab to a chemotherapy regimen improved PFS and objective response rate among patients with platinum-resistant recurrent ovarian cancer, according to findings from the AURELIA trial.
In the open-label, phase 3 randomized trial, researchers sought to assess efficacy, safety and quality-of-life outcomes associated with combination chemotherapy and bevacizumab (Avastin, Genentech) for the treatment of platinum-resistant, recurrent ovarian cancer.
The analysis included 361 patients with histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer that progressed less than 6 months after the completion of platinum-based therapy.
Patients with refractory disease, those with history of bowel blockage and those who underwent more than two previous cancer treatments were excluded.
After the patients were matched with appropriate chemotherapy regimens (pegylated liposomal doxorubicin, weekly paclitaxel or topotecan), they were randomly assigned to single-agent chemotherapy (n=181) or chemotherapy with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks, n= 179) until progression, unacceptable toxicities or patient withdrawal of consent.
Patients who progressed while on chemotherapy alone were allowed to cross over to single-agent bevacizumab.
PFS determined by RECIST served as the study’s primary endpoint. Objective response rate, OS, safety and patient-reported outcomes served as secondary endpoints.
Researchers reported median PFS of 6.7 months among patients assigned bevacizumab and chemotherapy vs. 3.4 months for patients assigned chemotherapy alone (HR=0.48; 95% CI, 0.38-0.6). The objective response rate was 27.3% in the combination arm and 11.8% in the chemotherapy-alone arm.
Median OS was 16.6 months in the combination arm and 13.3 months in the single-agent chemotherapy arm (HR=0.85; 95% CI, 0.66-1.08).
Patients treated with bevacizumab were more likely to develop grade ≥2 hypertension and proteinuria. Gastrointestinal perforation was observed in 2.2% of bevacizumab-treated patients.
“AURELIA is the first trial, to our knowledge, demonstrating a significant PFS benefit of either a combination regimen or a biologic agent in platinum-resistant ovarian cancer,” the researchers wrote. “On the basis of the statistically significantly improved PFS, together with response rate and safety results, bevacizumab combined with chemotherapy should be considered a standard option in platinum-resistant ovarian cancer.”
Disclosure: The researchers report no relevant financial disclosures.
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In the AURELIA trial, patients with platinum-resistant disease received single-agent chemotherapy with or without bevacizumab. Patients who received bevacizumab demonstrated a significant increase in response rate (27.3% vs 11.8%) and a doubling of median PFS (HR=0.48). There was a trend toward improved OS but, as in the case of the other three trials, no statistically significant difference was observed.
This lack of an OS advantage has created controversy about whether adding bevacizumab produces a true clinical benefit. The FDA, in similar circumstances, withdrew its approval of bevacizumab in breast cancer when a significant PFS improvement did not lead to a significant improvement in OS. The FDA has yet to review the ovarian cancer data.
The debate about PFS as an appropriate regulatory endpoint fails to take into account the confounding effect of extensive post-progression therapy. Both breast cancer and ovarian cancer are responsive to a number of available agents in the second- and subsequent-line treatment setting. Prior to the availability of such agents, phase 3 trials demonstrated a consistent positive correlation between PFS and OS in ovarian cancer. The only exceptions occurred in trials in which effective second-line therapy was available and utilized extensively. The failure to account for this in regulatory considerations will eventually threaten future drug development for these two important cancers in women.