Ask the Expert

by Alice Spinelli, NP

Alice Spinelli has worked a nurse practitioner since 1982, with the majority of her experience and interest in gynecologic oncology. She has been a member of the Ovarian Cancer National Alliance’s Scientific and Medical Advisory Board since 2004, and has authored several articles on gynecologic cancers for public and professional publications.

What were some important research findings or developments in ovarian cancer in 2012? Will new findings (such as the research presented at the 2012 ASCO meeting) change current treatments for ovarian cancer?

There have been encouraging research findings presented this year with regard to the treatment of ovarian cancer. Researchers are exploring several ways of augmenting the standard treatment with taxol and carboplatin, including: “dose dense” treatment with weekly taxol and every-three-week Carboplatin; the addition of other agents, including PARP inhibitors prior to and following standard chemotherapy (see below for more on PARP inhibitors); adding Avastin to standard treatment; and the potential risks and benefits of maintenance therapy.

There are also ongoing efforts to individualize care based on the patient’s tumor characteristics. Improved understanding of cancer genetics has set the stage for new clinical trials in this area. At the American Society of Clinical Oncology (ASCO) meeting Dr Douglas Levine led a session highlighting findings of the Cancer Genome Atlas project, which included a focus on ovarian cancer. One of the most challenging questions about managing cancer is why some patients respond to a given treatment better than others. Increased understanding of the genetic makeup of responders—and non-responders—may enable oncologists to better match patients and treatments.

Dr. Levine cited PARP inhibitors as one example of how genetic evaluation of a patient’s cancer could affect future research and practice. PARP (short for poly ADP ribose polymerase) is an enzyme that repairs damaged DNA and can behave as a backup enzyme to those produced by BRCA genes. Inhibiting PARP from its role in repairing a tumor’s DNA has been shown to be effective in treating breast and ovarian cancers in women with BRCA mutations. More recently PARP inhibitors have also demonstrated a benefit in treating ovarian cancer in women who are not BRCA mutation carriers.

This year has also brought surgical advances. The Society of Gynecologic Oncology developed a consensus statement on robotic-assisted surgery in gynecologic oncology. Robotically assisted surgery has had a significant impact on the minimally invasive surgical approach to patients with gynecologic malignancies and has been widely embraced by gynecologic oncologists in the United States. To date, experience has been primarily in the surgical management of endometrial and early cervix cancers. While there is less experience with ovarian cancer, the robotic technique may prove to be most appropriate in early stages. In exploring quality of life issues, one study found that six weeks after surgery women reported advantages to minimally invasive surgery, including better physical functioning and body image, less pain and an earlier return to normal activities. Another advantage may be the ability to begin or resume chemotherapy sooner.

We’ve been hearing about Avastin for a few years now—has the drug been approved in ovarian cancer?

Avastin (or Bevacizumab) has been shown to be effective in the treatment of ovarian cancer. As there have successful phase III clinical trials, Avastin is listed on the National Comprehensive Cancer Network (NCCN) compendium for the treatment of ovarian cancer. However, ovarian cancer is not yet listed as an FDA approved site for Avastin.

There was much media coverage last year in response to the FDA’s revoking accelerated approval of Avastin in the treatment of metastatic breast cancer. This decision had to do with the demonstrated benefit not justifying the potential risks, and not helping women live longer or with improved quality of life (QOL). Studies continue and Avastin will be considered again once there is further data to support its benefit. The ovarian cancer community should not be discouraged by this decision. Rather, it should be encouraged and reassured knowing the FDA objectively evaluates safety and QOL concerns.

What does it mean when a study shows an improvement in progression-free survival (PFS) but not in overall survival (OS)? Will the FDA approve a drug that shows an improvement in PFS but not OS?

First, some definitions: progression-free survival (or PFS) is defined as the length of time during and after the treatment of a disease that the patient lives with the disease without it progressing. We clinically describe this as stable disease, measured by how the patient feels (most important!), physical exams, diagnostic tests such as CT or PET scans, and/or CA125. Overall survival, (or OS) measures the specific length survival after treatment.

Both PFS and OS are important in evaluating how well a new treatment works. While using OS as a study end-point is the “gold standard,” studies that have PFS as and endpoint are very important as well. If a study shows improvement in PFS and not OS, it means the treatment was beneficial in controlling the disease for a significant amount of time; however, it did not demonstrate a benefit in how long those who received the treatment lived.

One advantage to measuring PFS is that it is not influenced by treatments received after the study treatment has ended, eliminating potential for bias created by response to subsequent treatments. In addition, results are available earlier than when measuring OS. PFS may also act as a surrogate for survival and predict OS. Both studies allow the opportunity to also measure treatment affect on QOL as secondary endpoints.

As to whether the FDA will approve drugs that demonstrate benefit in PFS but not OS, I have written and asked how they would respond to this question and am awaiting a reply. (Once received, I will then share it with The Teal Journal). The FDA does have a rigorous drug approval process that evaluates the efficacy and safety of a drug. They also consider the potential benefit to a specific disease. They do not consider the cost of a drug in their decision p