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Expert Explains Evolving Options in Frontline Ovarian Cancer

Gina Columbus @ginacolumbusonc
Published: Friday, Jan 11, 2019

Joyce F. Liu, MD, MPH

Joyce F. Liu, MD, MPH

With the emergence of new frontline regimens in ovarian cancer, Joyce F. Liu, MD, MPH, explained that the key for future research is for broader groups of patients to benefit and eventually be cured with systemic therapies.

In 2018, there were 2 key first-line approvals in ovarian cancer. In June, the FDA approved bevacizumab (Avastin) in combination with carboplatin and paclitaxel, followed by bevacizumab monotherapy, for the treatment of patients with advanced disease after initial surgical resection.

The PARP inhibitor olaparib (Lynparza) was approved in December as a maintenance treatment for patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to frontline platinum-based chemotherapy.

Next steps are to build upon chemotherapy backbones and combine PARP inhibitors, checkpoint inhibitors, and antiangiogenics together in an effort to improve survival for more patient subgroups.

“The key takeaways about newly diagnosed ovarian cancer and how we treat it with chemotherapy nowadays is that there are a number of options,” said Liu. “We still think about carboplatin and paclitaxel as our backbone, but there are a number of considerations that we now give as we meet women with newly diagnosed cancer.”

In an interview during the 2018 OncLive® State of the SummitTM on Ovarian Cancer, Liu, director of Clinical Research, Division of Gynecologic Oncology, assistant professor of Medicine at Dana-Farber Cancer Institute, highlighted the recent changes in the newly diagnosed ovarian cancer space and what the oncology field could see by the end of 2019.

OncLive: What are the key considerations in the newly diagnosed ovarian cancer space?

Liu: One [consideration] is when to give chemotherapy. Is it after surgery? Do we start chemotherapy before we do surgery, or do surgery and then give chemotherapy?

The second [takeaway] is, do we consider intraperitoneal chemotherapy? This is something that, in 2006, was considered to be potentially a standard of care that we should think about. However, new studies have brought into question whether this is as effective as we thought it once was.

The third is, how do we give this chemotherapy? Do we give it on a weekly basis or do we give it every 3 weeks? New studies have given us a better understanding of this. Then, what can we add to chemotherapy to make it more effective? Should we add bevacizumab? Should we think about maintenance therapy? PARP inhibitors are of very large interest right now, and there are very promising and interesting data in BRCA-mutation carriers with maintenance PARP inhibitors.

Looking beyond where we are today to where the clinical trials are taking us, [we need] to understand with the addition of antiangiogenic agents, the addition of PARP inhibitors, and immunotherapies, can we make our backbone therapy better than what it has been?

You brought up bevacizumab. Could you discuss the 2018 FDA approval of bevacizumab in the upfront setting and what impact it has had thus far?

Bevacizumab in upfront treatment of patients with ovarian cancer is an interesting question. The initial studies with bevacizumab were published in 2011, and consistently in the studies, we have seen somewhere between the 2- to 4-month progression-free survival (PFS) benefit but no overall survival (OS) benefit in the overall study populations. When we think about whether we are benefitting our patients, we give bevacizumab with chemotherapy and then maintenance bevacizumab for another year. Trading potential toxicities for a potential 2- to 4- month PFS benefit in everybody may not be the best decision. The question is, “Are there patients who benefit more [from bevacizumab]?”

[There are] subset analyses, but the caution with them is that these are subset analyses. The ICON7 and GOG-0218 study suggest that patients with high-risk disease or stage IV cancer may benefit from bevacizumab, but I don’t think we know that for certain. As we have been looking further into these studies, we have been looking for molecular markers that will tell us whether patients will benefit more. There are potential biomarkers, but nothing that has been validated.

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