Treating advanced cervical cancer: an interview with Dr. Krishnansu Tewari

Interview conducted by April Cashin-Garbutt, MA (Editor)Apr 9 2014

Please can you give a brief introduction to cervical cancer and how many women it affects?

Cervical cancer affects approximately 500,000 women every year globally of which 250,000 die annually, making it the 2nd leading cause of cancer-related death in women.

Although there are only 12,000 new cases in the United States each year because of successful screening and vaccination programs, still 4,000 women die each year from this disease in the US.

Unlike many other cancers, cervical cancer affects younger women who are often in the prime years of their lives and careers with young children at home.

How is advanced cervical cancer defined?

Advanced cervical cancer is a term that includes three populations of patients with cervical cancer:

1. those whose disease relapses after initial treatment with surgery and/or chemoradiation;
2. those whose disease does not completely go away and remains persistent after standard treatment with surgery and/or chemoradiation;
3. those patients who at the time of diagnosis are found to have cancer spread to distant organs and sites of the body far from the cervix (eg., the lungs, the lymph nodes in the neck, etc).

What treatment options are currently available for women with advanced cervical cancer?

Currently chemotherapy is the only available treatment option for women with advanced cervical cancer and not only is chemotherapy rarely if ever curative in this situation, but in those patients who may respond to the treatment, the response is relatively short-lived and the patient’s disease may progress rapidly and ultimately result in death within 8 months in real-world terms.

Please can you outline your recent research that was published in the New England Journal of Medicine?

We studied a drug that prevents the cancer from nourishing itself through blood vessel connections to the patient.

This drug prevents the process of forming the blood vessels which is called angiogenesis. Therefore, this drug is an anti-angiogenesis drug and by combining this to chemotherapy we hoped to help women with advanced cervical cancer live longer. This drug that we studied is called bevacizumab.

What were the main findings of this study?

The main findings of the study is that the Overall Survival of patients treated with chemotherapy plus bevacizumab was nearly 4 months longer than those treated with chemotherapy alone.

Importantly, the statistically significant improvement in Overall Survival did not come at the cost of significant deteriorations in quality of life. In addition, the side effects of the drug were manageable and occurred in <10% of patients with the exception of temporary high blood pressure which did not lead to treatment discontinuation in any patients.

Furthermore, no new side effects were discovered in association with this drug. Finally, even when there was relapsing cancer in the pelvis (which often had been previously irradiated for primary therapy), the drug continued to work.

Do you think that this trial suggests we may be on the cusp of converting this disease to a more chronic condition?

I believe this is the case. The problem with this patient population is that they are usually very sick and therefore are unable to tolerate more than one line of chemotherapy before they die. Patients with other cancers can be managed with multiple lines of chemotherapy for years, but not women with advanced cervical cancer.

However, with the near 4-month improvement in Overall Survival that was discovered when chemotherapy was combined with bevacizumab, we have for the first time identified a therapeutic window through which patients may benefit from being treated with other unique drugs such as other anti-angiogenesis drugs as well as novel drugs that stimulate the immune system.

The fact that quality of life was preserved for these patients receiving chemotherapy and bevacziumab further emphasizes the ability to continue treatment with other drugs that are as we speak coming down the National Cancer Institute’s drug discovery pipeline.

What do you think the future holds for treatments for advanced cervical cancer?

Based on the paper in the New England Journal of Medicine, the London Guardian reported nearly 2 weeks ago that the Cancer Drug Fund had released bevacizumab so that patients with advanced cervical cancer in England can receive it.

I am hopeful that the US FDA and the European Medicines Agency will also approve the drug for advanced cervical cancer. This is very important in the United States because the US FDA regulatory process is the only way patients receiving Medicaid and/or Medicare will be able to receive it.

Already because the chemotherapy regimen including bevacizumab has been listed by the National Comprehensive Cancer Network July 2013 updated treatment practice guidelines for cervical cancer, many HMOs and PPOs have been covering the drug for advanced cervix cancer patients.

I believe in the future nearly all women with advanced cervical cancer will receive an anti-angiogenesis drug like bevacizumab.

Where can readers find more information?

Readers are encouraged to read the original article in the New England Journal of Medicine as well as search online and review the stories that appeared recently on many prominent websites.

Included among these are press releases by the National Cancer Institute and the Gynecologic Oncology Group (now known as NRG).

About Dr. Krishnansu Tewari

Krishnansu Tewari, MD, is a board-certified gynecologic oncologist and a professor at the University of California, Irvine.

He earned a BS in molecular biology at the University of California, Berkeley, and then attended medical school at the University of California, Irvine, where he also completed his OB/GYN residency and his fellowship in gynecologic oncology.

Dr. Tewari is currently director of research in gynecologic oncology, co-chair of the cancer center’s Clinical Trials Protocol Monitoring and Review Committee, and principal investigator of the NRG (formerly Gynecologic Oncology Group).

He is also the director of the gynecologic oncology program at the St. Joseph Hospital Center for Cancer Prevention and Treatment.

He is the Chairman of the Society of Gynecologic Oncology’s Publications Committee and is a voting member of the NRG’s Cervix and Vulvar medicine committee and the Committee on Experimental Medicine.

Dr. Tewari is recognized nationally for his contributions to both robotic oncologic surgery and the conduct of clinical trials in gynecologic malignancies.

Dr. Tewari is the study chair and the principal investigator for the world’s first phase III randomized clinical trial of anti-angiogenesis therapy for cervical cancer. This study met its primary endpoint and showed a statistically significant improvement in overall survival when chemotherapy was administered with bevacizumab.

The paper was published on February 20, 2014 in the New England Journal of Medicine and in March 2014 bevacizumab was approved by the United Kingdom for women with advanced cervical cancer.

In 2010 Dr Tewari received National Institutes of Health funding for his translational research involving surrogate markers of angiogenesis and DNA repair enzymes. He is also the recipient of a Young Investigator Award by the Gynecologic Oncology Group and recently has been awarded two grants to study robotic surgery by Intuitive Surgical, Inc. 

Dr. Tewari has published more than 80 peer-reviewed papers and numerous book chapters and is on the editorial boards of Gynecologic Oncology and Women & Cancer magazine.