Roxanne Nelson

June 02, 2012

June 2, 2012 (Chicago, Illinois) — Bevacizumab (Avastin) combined with standard chemotherapy significantly increased progression-free survival in women with platinum-resistant ovarian cancer.

Researchers report that in these patients with ovarian cancer, adding bevacizumab to chemotherapy produced "statistically significant and clinically meaningful improvement" in both progression-free survival and overall response rate, compared with chemotherapy alone.

The results of the AURELIA trial, which is the first randomized trial of bevacizumab in platinum-resistant ovarian cancer, was presented here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO).

These patients represent an unmet clinical need, said Carol Aghajanian, MD, chief of the gynecologic medical oncology service at Memorial Sloan-Kettering Cancer Center in New York City, and a member of the ASCO Cancer Communications Committee.

"They have a low level of response. This is the first trial to show improvement in this group of patients," said Dr. Aghajanian, who moderated a press briefing during which highlights of the trial were presented.

At a median follow-up of 13.5 months, only 75% (135 of 179) of patients who received bevacizumab plus chemotherapy experienced disease recurrence, compared with 91% (166 of 182) of patients who received chemotherapy alone.

Overall response rate was better with the combination (30.9%; 95% confidence interval [CI], 24.1 to 38.3) than with chemotherapy alone (12.6%; 95% CI, 8.0 to 18.4).

Median progression-free survival was longer with the combination than with chemotherapy alone (6.7 vs 3.4 months). Overall survival data are not yet complete, according to the researchers.

This combination "halves the risk of worsening disease," said lead study author Eric Pujade-Lauraine, MD, PhD, from the Université de Paris Descartes, France, and head of the Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO). "Bevacizumab plus chemotherapy should be considered a new standard option for patients with platinum-resistant ovarian cancer."

Platinum-based chemotherapy is commonly used in ovarian cancer, but not all patients respond and the disease can become resistant to it, he noted. "These patients have not had many treatment options."

Bevacizumab has shown activity in ovarian cancer in other large trials, said Dr. Pujade-Lauraine. "But AURELIA is the first phase 3 trial in this difficult-to-treat group of patients."

ICON7 and OCEANS

Previous studies have shown that bevacizumab is active in the first- and second-line treatment of ovarian cancer. As previously reported by Medscape Medical News, the ICON7 trial showed that adding bevacizumab to standard chemotherapy can offer a survival benefit for women with newly diagnosed ovarian cancer.

In ICON7, at a median follow-up of 28 months, there were fewer deaths in patients who received bevacizumab plus chemotherapy than in those who received standard chemotherapy (178 vs 200). Although this represents a 15% overall reduction in mortality risk, the difference did not reach statistical significance (hazard ratio [HR], 0.85; P = .11).

In an updated analysis, patients who received the combination had longer progression-free survival than those who received chemotherapy alone (19.8 vs 17.4 months; HR, 0.87; P = .039).

The OCEANS trial showed that bevacizumab plus chemotherapy (carboplatin and gemcitabine) followed by bevacizumab until disease progression provides a clinically meaningful benefit for patients with recurrent ovarian cancer. The addition of bevacizumab to a standard platinum-based regimen led to a 4-month improvement in median progression-free survival. In addition, there were significant improvements in the objective response rate and in the median duration of response.

In a second interim analysis of the OCEANS trial (with a cutoff date of August 29, 2011), there were 235 deaths (48.6%), the majority of which were caused by disease progression. In that analysis, median overall survival was 33.3 months with the combination and 35.2 months with chemotherapy alone.

An ovarian cancer expert has questioned how bevacizumab will be used if it is approved for use in ovarian cancer. "One of the comments that has been made by many is that although bevacizumab may be active in other tumors as a single agent, it is really impressively active in ovarian cancer for a variety of reasons...in terms of the normal ovarian cells and the role of angiogenesis in the normal physiology," he said. "It makes some sense, but the question is, is there any reason to give it with chemotherapy? We don't have the answer to that, of course, but the data that we see just continue to raise those questions," said Maurie Markman, MD, vice president of patient oncology services, and national director for medical oncology at the Cancer Treatment Centers for America.

Study Details

Dr. Pujade-Lauraine and colleagues randomized 361 patients with ovarian cancer that had progressed for 6 months or less after undergoing at least 4 cycles of platinum-based therapy from October 2009 to April 2011.

All patients received paclitaxel, topotecan, or liposomal pegylated doxorubicin, per investigator, and were randomly assigned to either chemotherapy alone or chemotherapy plus bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks, depending on type of chemotherapy). Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Those receiving chemotherapy alone were able to cross over to bevacizumab monotherapy at disease progression.

The primary end point was progression-free survival; secondary end points included objective response rate, overall survival, safety, and quality of life.

Adverse events were higher with the combination than with chemotherapy alone. These included grade 2 and higher hypertension (20% vs 7%), proteinuria (11% vs 1%), gastrointestinal perforations (2% vs 0%), and fistula or abscesses (2% vs 0%). Grade 3 and higher adverse events were similar between the 2 groups.

The study was sponsored by Roche. Dr. Pujade-Lauraine and several of the coauthors report financial relationships with industry, as noted in their abstract.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract LBA5002. Presented June 2, 2012.

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