Novel Frontline Regimens Are Emerging for Advanced Ovarian Cancer

Christin Melton, ELS
Published: Thursday, Aug 02, 2018
Bradley J. Monk, MD, FACOG, FACS
Bradley J. Monk, MD, FACOG, FACS
Over the past few years, the FDA has approved various medicines from several new drug classes to treat patients with ovarian, fallopian tube, and peritoneal cancers. Although most approvals occurred in the recurrent ovarian cancer setting, numerous studies are expected to present data in the coming year that may transform how clinicians manage newly diagnosed disease.

Ongoing clinical trials are investigating the frontline use of PARP inhibitors, immunotherapies, and targeted agents and how to combine these drugs with each other and with standard chemotherapy. During an OncLive Peer Exchange® panel discussion, moderator Bradley J. Monk, MD, and other gynecologic oncology experts from across the United States talked about how new evidence has affected their approach to treating advanced ovarian cancer.

They also debated the potential benefits and obstacles to incorporating bevacizumab (Avastin) into frontline regimens. Shortly after the panel session, the FDA approved bevacizumab as an add-on to adjuvant carboplatin and paclitaxel (Abraxane) for patients with advanced ovarian, fallopian tube, or peritoneal cancer.

Because advanced ovarian cancer has a high risk of recurrence and mortality, Monk said, “It is paramount to understand optimal management of this disease and how to achieve the best outcomes for each individual patient in a first-line fashion.”

Neoadjuvant Choices

Before any treatment decisions are made, it is paramount to fully stage the patient, including omentectomy and lymph node dissection, stressed panelist Matthew Powell, MD. He said despite the importance of full staging to identify patients more likely to benefit from aggressive therapies, “it’s not widely done across communities.” If staging confirms a patient has advanced disease, the next decision is whether to proceed with neoadjuvant chemotherapy (NADT) or primary debulking surgery (PDS). Because patients who begin with NADT ultimately have surgery, David M. O’Malley, MD, said all patients with advanced disease should be referred to a gynecologic oncologist before treatment, a position consistent with joint treatment guidelines from the American Society of Clinical Oncology (ASCO) and the Society of Gynecologic Oncology.1 The guidelines recommend NADT for women unfit for PDS or for whom complete cytoreduction is unlikely.1

Ursula A. Matulonis, MD, said several trials have shown NADT offers similar progression- free survival (PFS) and overall survival (OS) outcomes to PDS. For example, at this year’s ASCO Annual Meeting (ASCO 2018), findings from 2 randomized phase III trials showed no significant difference in survival outcomes between NADT and PDS in women with advanced ovarian cancer.2,3 However, NADT was beneficial for women with poor performance status. “It’s really been one of the breakthroughs, that chemotherapy can convert an inoperable patient to an operable patient, and it certainly changed my practice in almost half the cases,” Monk said.

A recent study investigated whether adding hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes in women with unresectable advanced ovarian cancer who received NADT.4 Shannon N. Westin, MD, MPH, said that in the group of patients who received HIPEC at the time of debulking surgery, PFS was about 4 months longer and OS was about 11 months longer than in the group of patients who did not receive HIPEC. Westin said although the investigators said the safety profile was about the same between the 2 groups, a closer look at surgical outcomes showed a much higher rate of colostomy or ileostomy in patients who received HIPEC. “[Colostomy] wasn’t something that was mandated, and they don’t really have a good explanation for it,” she said. The panelists largely agreed they wanted more evidence of HIPEC’s efficacy before recommending it to patients.

Bevacizumab in the Frontline

In March 2018, the National Comprehensive Cancer Network (NCCN) updated its guidelines for ovarian cancer.5 Powell, an NCCN panelist, explained that the NCCN downgraded several treatment recommendations because when cost and toxicity were factored in, there was insufficient evidence to support one approach over another. Thus, intraperitoneal and dose-dense weekly chemotherapy were downgraded from category 1 to 2a, whereas bevacizumab was upgraded from 2b to 2a.5

In 2011, findings from the ICON7 and GOG-0218 phase III trials established that adding bevacizumab to chemotherapy and continuing bevacizumab for several cycles after chemotherapy improved PFS in patients who underwent initial resection of advanced ovarian cancer.6,7

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