Adding Bevacizumab to Chemo Boosts Survival in Advanced Cervical Cancer


By Anne Harding

NEW YORK (Reuters Health) - The overall survival (OS) benefit seen with bevacizumab in advanced cervical cancer persists with extended follow-up, new research shows.

“We saw a significant improvement in overall survival when Avastin (bevacizumab) was combined with chemotherapy a few years ago, but that was based on an interim analysis,” Dr. Krishnansu Tewari of the University of California, Irvine Medical Center, in Orange, told Reuters Health by telephone. “Many of us wondered if that survival impact would persist with longer follow-up, and sure enough it did.”

The findings were published online July 27 in The Lancet.

The Gynecologic Oncology Group (GOG) 240 trial also identified a new toxicity - fistula - which was more likely to occur in patients who received bevacizumab, and was seen only in patients who had previously received pelvic radiotherapy.

The U.S. Food and Drug Administration approved bevacizumab for advanced cervical cancer in 2014, after the results of the interim analysis of the GOG 240 trial were reported in 2012. Sixty countries worldwide approved the drug based on the results.

The GOG 240 trial included 452 patients from 81 centers in the U.S., Canada and Spain, who were randomly assigned to one of four groups: cisplatin plus paclitaxel or toptecan plus paclitaxel, with or without bevacizumab.

At follow-up of more than 50 months, OS was 16.8 months for patients who received bevacizumab and chemotherapy versus 13.3 months for patients who only received chemotherapy. For patients who had not received pelvic radiotherapy, overall survival was 24.5 months, compared with 16.8 months for those who did receive radiation.

In the bevacizumab groups, 15% of patients developed fistulas, all of whom had received pelvic radiation previously, with 6% having clinically severe fistula (compared to <1% of the chemotherapy-alone groups). None of the fistulas was associated with sepsis, death, or emergency surgical intervention.

“Approval of Avastin for this patient population has been great because it has provided an option for patients when there were really never very good options,” Dr. Tewari said. “The negative side is it has created a new group of patients, the patients who progress on Avastin.”

He added: “Clinicians have to weigh the risks and benefits of this treatment, and counsel patients about the risks of fistula and other side effect(s).” While the survival advantage of 3.5 months is “modest,” he noted, “to some patients it may be justifiable.”

Dr. Tewari and his colleagues are about to launch a phase 3 randomized clinical trial of immunotherapy with checkpoint inhibitors that will include cervical cancer patients who have progressed on bevacizumab.

Dr. Susana Banerjee, a consultant medical oncologist at The Royal Marsden in London who wrote an editorial accompanying the study, said, “The addition of bevacizumab to chemotherapy is a step forward in improving survival for women with cervical cancer.”

“Survival was extended by a median of 3.5 months in a devastating condition where most women in this situation (non-curative) survive for around 12 months,” she told Reuters Health by email. “We must not forget that cervical cancer is a preventable and curable condition in many cases, and therefore it is imperative that there is a worldwide focus on cancer prevention strategies (HPV vaccination, screening).”

She added: “There is an urgent need to improve treatments beyond bevacizumab. The survival of women whose disease has worsened after bevacizumab in combination with chemotherapy was only around 8 months. There are several promising approaches of other targeted therapies and immunotherapy in ongoing and planned clinical trials. We need to further identify patients who are most likely to derive the greatest survival benefit from antiangiogenic therapy with the least risk.”

The study was funded by the National Cancer Institute. Dr. Tewari and several coauthors reported ties to Genentech, which markets Avastin.


Lancet 2017.

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