The addition of bevacizumab (Avastin, Genentech/Roche) to chemotherapy prolongs survival in women with advanced cervical cancer by about 4 months, compared with chemotherapy alone, according to a phase 3 trial published in the February 20 issue of the New England Journal of Medicine.
The results were described as "practice changing" when they were first presented during the plenary session at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO).
As it turned out, the findings changed practice almost as soon as they were presented.
A month after the ASCO meeting, the National Comprehensive Cancer Network (NCCN) updated their cervical cancer clinical practice guidelines to include bevacizumab plus chemotherapy as an adjuvant treatment, explained lead author Krishnansu Tewari, MD, professor of obstetrics and gynecology at the University of California, Irvine.
"With the NCCN listing, many patients from HMO and PPO insurance plans are able to get the drug for this indication," he told Medscape Medical News.
"If the FDA decides to approve this drug for advanced cervical cancer, patients with Medicare and Medicaid will be able to receive it as well. Then I'll be happy," he added.
This year, the manufacturer will file for approval in advanced cervical cancer in the United States and globally, a company spokesperson told Medscape Medical News.
Clinically Meaningful Benefit
In the study population, median overall survival was better with bevacizumab than with chemotherapy alone (17.0 vs 13.3 months; hazard ratio [HR], 0.71; P = .004).
All participants had recurrent, persistent, or metastatic disease. During the median follow-up of 20.8 months, 60% of the patient population died.
The improvement in survival is "clinically meaningful," the authors write.
"Historically, this is a patient population that does not respond to anything in a meaningful way," said Dr. Tewari. "What I mean is that patients with advanced cervical cancer may have some tumor shrinkage with chemotherapy, but this lasts for perhaps a month and then the cancer progresses and these patients die," he explained.
Progression-free survival was also significantly better with bevacizumab than with chemotherapy alone (8.2 vs 5.9 months; HR for disease progression, 0.67; 95% CI, 0.54 - 0.82), as was the response rate (48% vs 36%; P = .008).
"These data are very favorable, compared with what bevacizumab has achieved in the treatment of other cancers," said Gottfried Konecny, MD, from the David Geffen School of Medicine at the University of California, Los Angeles, at the ASCO meeting.
Information on Adverse Events
The Gynecologic Oncology Group (GOG) 240 trial was funded by the National Cancer Institute (NCI). It involved 452 patients with pretreated advanced cervical cancer who were treated from 2009 to 2012 in Spain and the United States. Most had recurrent disease (72%); a minority had persistent disease (11%).
Patients were randomly assigned to 1 of 4 treatment groups: topotecan plus paclitaxel with or without bevacizumab; and cisplatin plus paclitaxel with or without bevacizumab.
The analysis conducted in 2012 revealed that topotecan plus paclitaxel was not superior to cisplatin plus paclitaxel, and the investigators and patients were notified of the finding at that time, according to the NCI.
Intravenous bevacizumab 15 mg/kg was administered once every 3 weeks at the same time as the chemotherapy until disease progression or unacceptable toxicity occurred.
Of the patients who received bevacizumab, 28 had a complete response; of those who received chemotherapy alone, 14 had a complete response (P = .03). Treatment was discontinued in 21 patients who had a complete response.
However, the addition of bevacizumab to chemotherapy led to more adverse effects.
Hypertension of grade 2 or higher was significantly more common in those treated with bevacizumab than in those who were not (25% vs 2%, P < .001), but no patients discontinued bevacizumab because of hypertension, the authors point out.
Gastrointestinal or genitourinary fistulas of grade 3 or higher were significantly more common in those treated with bevacizumab than in those who were not (6% vs 0%; P = .002), as were thromboembolic events of grade 3 or higher (8% vs 1%; P = .001).
Fatal adverse events were the same in those treated with bevacizumab and those who were not (1.8% vs 1.8%).
Although there was a numerical decrease in health-related quality-of-life scores in patients who received bevacizumab, the difference was not statistically significant.
The GOG 240 trial was sponsored by the NCI. Genentech provided support for the trial under the Cooperative Research and Development Agreement (CRADA) with the NCI for the clinical development of bevacizumab.
N Engl J Med. 2014;370:734-743. Abstract
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Cite this: Bevacizumab Changes Practice in Advanced Cervical Cancer - Medscape - Feb 19, 2014.