Bevacizumab prolongs survival in advanced cervical cancer, UCI Health-led trial finds

Results have already changed treatment guidelines

Women with advanced cervical cancer now have a new treatment option that could lengthen their lives. A trial led by UC Irvine gynecologic oncologist Dr. Krishnansu S. Tewari found that combining chemotherapy with bevacizumab, also known as Avastin, extended median survival to 17 months, compared to 13.3 months for those receiving chemotherapy without bevacizumab.

Furthermore, treatment with the anti-angiogenesis drug — which inhibits a tumor’s ability to form new blood vessels — caused no significant deterioration in quality of life. The results of the phase 3 randomized trial conducted by the Gynecological Oncology Group appear in today’s issue of the New England Journal of Medicine.

“This trial showed for the first time that a targeted agent could improve overall survival in a gynecologic cancer,” said Tewari, a professor of obstetrics & gynecology at the University of California, Irvine. “Women with metastatic or recurrent cervical cancer don’t have many options, and now we finally have a therapy that helps them live longer.”

Although a difference of 3.7 months may not seem like a long time, Tewari said it is important to understand that this patient population responds very poorly to even one line of therapy and that those minimal responses tend to be short-lived.

“We do not have the luxury of treating women who have advanced cervical cancer with multiple lines of therapy over many years, as we do with more [chemotherapy] sensitive malignancies such as ovarian or breast cancer,” Tewari said. “However, these findings show that we may be on the cusp of converting this disease from a terminal to a chronic condition where the 3.7 months provides a window of opportunity in which patients might benefit from new therapies, including other anti-angiogenesis drugs and immunotherapies that are now being studied.”

Cervical cancer is one of the most common cancers worldwide and is responsible for at least 250,000 deaths annually. Although screening with Pap smears and high-risk HPV DNA testing has reduced the incidence and mortality in the U.S., each year about 12,000 U.S. women are diagnosed with the disease and more than 4,000 die of it.

“The vast majority of these deaths are young women in the prime of their lives and often with young children,” Tewari said. “This study population represents an underserved group who often lack healthcare insurance or access to potentially lifesaving cancer screening and treatment.”

He called the trial results a “triple-header.” Among patients who received bevacizumab along with chemotherapy:

• There was a “highly statistically significant” difference in overall survival — a median of 3.7 months.
• The response rate, or the percentage of patients whose cancer shrank or disappeared after treatment, was better — 48 percent versus 26 percent.
• Progression-free survival, or the length of time during and after treatment a patient lives with the disease but it does not get worse, also was better — 8.2 months compared with 5.9 months.

According to the National Cancer Institute, the trial was designed to answer two questions: whether topotecan in combination with paclitaxel was superior to cisplatin in combination with paclitaxel, and whether the addition of bevacizumab to either regimen improved overall survival. Patients were randomly assigned to one of four treatment groups, two of which received bevacizumab.

Serious adverse events (grade 3, 4), including blood clots and fistulas, occurred in less than 10 percent of patients getting bevacizumab. No new adverse events associated with the drug were discovered.

The trial enrolled 452 patients in the United States and Spain with metastatic, recurrent or persistent cervical cancer not curable with standard treatment between 2009 and 2012.

The findings have already changed U.S. treatment for advanced cervical cancer. Within a month of the study’s presentation at the June 2013 meeting of the American Society of Clinical Oncology, the National Comprehensive Cancer Network listed the cisplatin-paclitaxel-bevacizumab triplet in the NCCN Cervical Cancer Treatment Guidelines Update.

Tewari said the NCCN listing now permits some patients with HMO and PPO insurance to complement their treatment with bevacizumab. Also, Medicare and Medicaid beneficiaries will be able to receive the drug for treatment of advanced cervical cancer if and when the U.S. Food & Drug Administration approves its use in that capacity. Drug manufacturer Genentech will file for approval.

The trial results concerning the non-superiority of the non-platinum chemotherapy doublet were first presented at the March 2013 annual meeting on women's cancer by the Society of Gynecologic Oncology; the presentation was the meeting’s No. 1 abstract and garnered the SGO Presidential Award for Most Outstanding Scientific Abstract as well as the coveted Hugh Barber Lectureship designation. The survival data concerning bevacizumab was later presented at the June 2013 American Society of Clinical Oncology annual meeting, the world's largest oncology meeting. The abstract was one of five of the more than 5,500 abstract submissions to be featured in the ASCO general plenary session.

The multiple center, multinational trial — known as GOG 240 — was conducted by the Gynecologic Oncology Group and was funded by the National Cancer Institute. Genentech provided support for the trial under the Cooperative Research & Development Agreement with NCI for the clinical development of bevacizumab.

Tewari, Dr. Robert E. Bristow, Dr. Leslie M. Randall and Dr. Michael L. Berman of UCI Health enrolled patients at UC Irvine Medical Center in Orange, Calif. Dr. Philip J. Di Saia, professor emeritus in the UCI Health Department of Obstetrics & Gynecology, was chair of the Gynecologic Oncology Group during the entire GOG 240 study period.

The National Cancer Institute leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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