Emerging Role for Bevacizumab in Platinum-Resistant Ovarian Cancer

Megan Brooks

May 02, 2014

Combining bevacizumab (Avastin) with standard chemotherapy eases symptoms in patients with platinum-resistant recurrent ovarian cancer, new results from the AURELIA trial confirm.

The study demonstrated that adding bevacizumab to chemotherapy led to a statistically significant improvement in progression-free survival and objective response rate over standard chemotherapy alone, but there was no overall survival benefit. It was led by Eric Pujade-Lauraine, MD, PhD, from the Université de Paris Descartes in France, and published in the May 1 issue of the Journal of Clinical Oncology.

Of note, patient-reported outcomes (PROs) described in an accompanying study demonstrate that bevacizumab increased the proportion of patients who achieved a 15% improvement in abdominal/gastrointestinal symptoms during chemotherapy. That study was led by Martin R. Stockler, MD, from the University of Sydney in Australia.

"It is noteworthy that AURELIA is the first study incorporating bevacizumab in ovarian cancer to report an improvement in PROs," note the authors of an accompanying editorial.

"In the setting of platinum-resistant ovarian cancer, in which therapy is palliative, improvement in PROs is of potential importance even in the absence of an overall survival benefit," write Joyce F. Liu, MD, MPH, from the Dana-Farber Cancer Institute, and Stephen A. Cannistra, MD, from the Beth Israel Deaconess Medical Center, both in Boston.

Results from the AURELIA trial, the first randomized trial of bevacizumab in platinum-resistant ovarian cancer, were first presented at the 2012 Annual Meeting of the American Society of Clinical Oncology, and reported at that time by Medscape Medical News.

A Standard Option

To recap, AURELIA involved 361 patients with measurable/assessable ovarian cancer that had progressed less than 6 months after the completion of platinum-based therapy.

Patients were randomly assigned to investigator-selected single-agent chemotherapy with once-weekly pegylated liposomal doxorubicin, paclitaxel, or topotecan (n = 182) or to chemotherapy plus bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks (n = 179) until progression, unacceptable toxicity, or consent withdrawal.

Median follow-up was 13.9 months in the chemotherapy group and 13.0 months in the bevacizumab group.

The AURELIA study met its primary objective by demonstrating significantly better progression-free survival in the bevacizumab group than in the chemotherapy group (6.7 vs 3.4 months; hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.38 - 0.60; P < .001).

The objective response rate was also significantly better in the bevacizumab group (27.3% vs 11.8%; P = .001).

However, there was no benefit in overall survival in the bevacizumab group, compared with the chemotherapy group (16.6 vs 13.3 months; HR, 0.85; 95% CI, 0.66 - 1.08; P < .174).

No new safety signals were observed.

"On the basis of the statistically significantly improved progression-free survival, together with response rate and safety results, bevacizumab combined with chemotherapy should be considered a standard option in platinum-resistant ovarian cancer," Dr. Pujade-Lauraine and colleagues conclude.

In their editorial, Drs. Liu and Cannistra say the AURELIA trial joins 3 other trials of bevacizumab for ovarian cancer in demonstrating improved outcomes with the addition of bevacizumab to standard chemotherapy. The margin of benefit in AURELIA is similar to that in the other 3 trials, "which suggests a remarkable consistency in the observed effects of combining bevacizumab with chemotherapy in several different settings in ovarian cancer," they write.

"Importantly, AURELIA also studied PROs as a separate preplanned secondary end point," they point out.

The PRO data show that more patients in the bevacizumab group achieved at least a 15% improvement in abdominal/ gastrointestinal symptoms at week 8 or 9 (21.9% v 9.3%), which is a difference of 12.7% (95% CI 4.4 - 20.9; P = .002).

"This finding was corroborated by sensitivity analyses using alternative PROs, assumptions, and statistical methods," Dr. Stockler and colleagues explain. "Effects on a broader range of quality-of-life [QoL] concerns either favored the bevacizumab group or were no different," they point out.

"Together, these findings suggest that the beneficial effects of bevacizumab on ovarian cancer symptoms were not outweighed by any additional toxicity detrimentally affecting QoL," the investigators report.

A Select Group

Drs. Liu and Cannistra say it's important to note that the patients enrolled in AURELIA were chosen because they had received no more than 2 previous lines of chemotherapy and did not have platinum-refractory disease. In addition, they did not have history of bowel obstruction, clinical signs of bowel obstruction, or evidence of bowel involvement, all of which increase the risk for bowel perforation with bevacizumab. Up to 11% of patients who met less stringent eligibility criteria experienced bowel perforation (J Clin Oncol. 2007;25:5180-5186), they point out.

"Consequently, if this regimen is to be considered in symptomatic patients with platinum-resistant disease, it would be important to adhere to similar eligibility criteria as those used in AURELIA," Drs. Liu and Cannistra advise.

They note that treatment guidelines for the use of bevacizumab in ovarian cancer differ around the world.

Bevacizumab is not currently approved by the US Food and Drug Administration for any indication in ovarian cancer. However, in the National Comprehensive Cancer Network guidelines, it is considered an acceptable agent in combination with carboplatin and gemcitabine in platinum-sensitive relapse.

Currently, the National Institute for Health and Care Excellence in the United Kingdom does not recommend bevacizumab for use in either newly diagnosed or recurrent ovarian cancer.

However, the European Medicines Agency has approved bevacizumab in combination with carboplatin and paclitaxel, along with subsequent maintenance single-agent bevacizumab, for patients with newly diagnosed ovarian cancer, as well as bevacizumab in combination with carboplatin and gemcitabine in platinum-sensitive relapse.

The AURELIA study was sponsored by Roche. Dr. Pujade-Lauraine and several of his coauthors report financial relationships with industry, which are listed with the study.

J Clin Oncol. 2014;32:1287-1289, 1302-1308, 1309-1316. Editorial, Pujade-Lauraine abstract, Stockler abstract


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