New Ovarian Cancer Guidelines Include Bevacizumab, Olaparib Approvals

Recent advancements in the treatment of ovarian cancer have led the National Comprehensive Cancer Network to make changes to their clinical practice guidelines in its 20th annual edition.

Recent advancements in the treatment of ovarian cancer, including the approvals of bevacizumab and olaparib, have led the National Comprehensive Cancer Network to make changes to their clinical practice guidelines in its 20th annual edition.

"There have been a number of advancements in the treatment of ovarian cancer since the first NCCN Guidelines were published in 1996," Robert J. Morgan Jr, MD, FACP, professor of medical oncology, Department of Medical Oncology and Therapeutics Research, City of Hope, and Chair, NCCN Guidelines Panel for Ovarian Cancer, said in a statement. “One major development is the recommendation for intraperitoneal chemotherapy in certain patient populations. Now a category 1 designation, this treatment recommendation was added to the Guidelines when strong evidence was published that showed this treatment approach to have a major improvement on the median survival in women."

Guideline changes were also made to sections referring to treating epithelial ovarian cancer, Fallopian tube cancer, and primary peritoneal cancer; less common ovarian histopathologies; malignant germ cell tumors; ovarian low malignant potential tumors; malignant germ cell and sex-stromal tumors; and to the International Federation of Gynecology and Obstetrics Guidelines of staging classification for ovarian cancer, Fallopian tube cancer, and peritoneum cancer.

The combined analysis of the GOG-172 and GOG-114 trials showed that patients treated with IP experienced a 16% reduction in the risk of progression compared with IV therapy. Additionally, IP chemotherapy led to a median overall survival (OS) of 62 months compared with 51 months for IV therapy.

However, this combination regimen causes more side effects than IV chemotherapy alone. Researchers are continuing to study lower doses and alternative drug approaches to try to produce similar benefits with fewer side effects.

Surgery surrounding ovarian cancer has also improved over the years, said Morgan, who has served as the NCCN Guidelines Panel Chair for Ovarian Cancer for 20 years.

In the guidelines’ original version, he explained, there was marked disagreement regarding the role of complete surgical staging in low-stage cancer with a category III recommendation.

"Since that time, the role of surgery has become clearer, and complete surgical staging and/or debulking is now recommended for virtually all patients who are suspected of having any residual disease,” Morgan said.

European studies have demonstrated that upfront cytoreductive surgery is associated with a survival advantage compared with cytoreductive surgery after three cycles of chemotherapy.

Another significant update in the field of ovarian cancer was the November 2014 approval of bevacizumab (Avastin) in combination with chemotherapy for patients with platinum-resistant recurrent ovarian cancer.

“Avastin plus chemotherapy is the first new treatment option for women with this difficult-to-treat type of ovarian cancer in more than 15 years,” Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, said at the time of the approval. “Risk of the disease worsening was reduced by 62% for women who received Avastin plus chemotherapy in the study, and a notable treatment effect was observed with paclitaxel, which may be important when choosing treatment.”

The FDA approval was based on the phase III AURELIA trial, which demonstrated a median progression-free survival (PFS) with bevacizumab of 6.8 versus 3.4 months with chemotherapy alone (HR = 0.38;P<.0001).

Because improvement in PFS rather than OS may be an acceptable treatment outcome, explained Morgan, bevacizumab-containing regimens are listed; however, these regimens may have differing category 2A, 2B, or 3 recommendations due to the strength of published evidence showing an improvement, depending on when in the course of treatment the regimens are used.

The guidelines were updated to also include olaparib (Lynparza), which was approved in December 2014. The PARP inhibitor is approved to treat patients withBRCA-positive advanced ovarian cancer following treatment with three or more cycles of chemotherapy.

The FDA approval was based on a single-arm phase II study, which demonstrated a 34% objective response rate (ORR), with a 7.9-month duration of response, seen in 137 patients.

"NCCN is proud to have played a role in the advancement treatment of women with ovarian cancer since the first NCCN Guidelines were published in 1996," Robert W. Carlson, MD, chief executive officer, NCCN, said in a statement. "We applaud Dr. Morgan and panel for their decades of service and dedication to improving the outcomes for women with such a deadly disease."