Sorting Through Unanswered Questions in Ovarian Cancer

Thanh H. Dellinger, MD

There are no clear indications driving which patients with newly diagnosed advanced ovarian cancer should receive intraperitoneal (IP) chemotherapy, dose-dense chemotherapy, or hyperthermic intraperitoneal chemotherapy (HIPEC); therefore, physicians currently rely on clinical features, patient characteristics, and even biases to make treatment decisions, explained Thanh H. Dellinger, MD.

Upfront surgery is still the gold standard, but if this approach isn’t feasible then it’s important to have a personalized discussion with each patient with ovarian cancer to highlight their potential options, added Dellinger, a gynecologic oncology surgeon and assistant professor in the Division of Surgery, City of Hope.

“Getting a good surgery is still the mainstay, and then getting all of the options offered to you as far as neoadjuvant therapy is important too,” noted Dellinger.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Dellinger provided insight on the treatment of patients with newly diagnosed advanced ovarian cancer.

OncLive: What is the current treatment paradigm for newly diagnosed advanced ovarian cancer?

Dellinger: Over the last 20 years, a number of clinical trials have proven that we can use IP chemotherapy and that there's a role for dose-dense chemotherapy. We can also treat with the addition of bevacizumab (Avastin). [Deciding] what setting to use any of these regimens in is complex and challenging. The clinical trials that have been done to date have only partly answered these questions.

From those clinical trials, what answers do we currently have?

The landmark trial for IP chemotherapy in ovarian cancer was GOG-172. This showed a survival benefit, both overall survival (OS) and progression-free survival (PFS), for patients with ovarian cancer who are optimally cytoreduced. Unfortunately, the most recent clinical trial in this setting, GOG-252, did not show an improvement. This may be in part due to the bevacizumab addition in those arms. Another clinical trial, iPocc, will hopefully give us some answers as this is accruing in Europe.

What are the unanswered questions that currently exist?

The unanswered questions are really: What is the role of dose-dense chemotherapy in ovarian cancer? Are there certain subpopulations that benefit from one regimen or the other? Do Asian patients benefit the most from IP chemotherapy, or do BRCA-positive patients? As we really progress more in clinical trials, we will probably better define who these patient populations are. Hopefully, we will be able to personalize therapy much more.

How do you address these types of questions in clinical practice?

Medicine is an art, and it's definitely something that needs to be individualized for the patient. I always tell my patients that if they went to 10 different oncologists, they would get 10 different answers. That is very true. What works in one patient may not work the same way due to different characteristics. There are also a lot of differences in the BRCA-positive patients and in those who undergo neoadjuvant chemotherapy. Therefore, it is an individualized counseling session.

What are the options for patients who undergo neoadjuvant chemotherapy?

Now, we have the option of delivering HIPEC. This is given at the time of interval cytoreduction, and existing evidence shows an OS and PFS benefit in patients who undergo HIPEC. However, just like IP chemotherapy, HIPEC is a complex procedure and is not a therapy that can be administered at every institution; not every community center is ready to give HIPEC. Unfortunately, especially in California, your insurance dictates what kind of therapy you can get.

What other patient characteristics would help you inform ovarian cancer treatment decisions?

Patients who are optimally cytoreduced should still receive IP chemotherapy; BRCA-positive patients will also do well with IP chemotherapy. Those who are sub-optimally cytoreduced may benefit more from bevacizumab, but Asian patients may benefit more from dose-dense chemotherapy.

At this time, it is still important for an individualized counseling session because there are still so many questions. For example, with IP chemotherapy, I will tell patients that [this approach] has shown some of the best long-term survival data.

On the other hand, it can be toxic. You want to make sure you're getting IP chemotherapy at an experienced center, where this a lot of experience both in terms of nurses and clinicians. For patients who are interested in HIPEC, I let them know it's a tough surgery because there may be some complications. Each of these modalities have their risks and side effects but also benefits. Those need to be carefully balanced with the patient's wishes and their individual disease.

Bias is definitely present in most physicians' practice. In a way, bias comes from what you think your personal strengths are. You may understand that your strength is that you can optimally cytoreduce patients, and that is your bias over neoadjuvant chemotherapy. You may understand your strength is that your institution does well with IP chemotherapy when other institutions may have failed [with the approach]. You have to operate with those strengths and also understand your weaknesses.

What would you consider to be your take-home message to other healthcare professionals treating patients with ovarian cancer?

The bottom line is that patients need to get to a good gynecologic oncology surgeon. Make sure patients are able to have an upfront surgery if feasible, or at least a very good work up to it. Once you found a good surgeon, the biggest thing is to get tested to figure out if you are a BRCA-mutated patient, for example. Then, you need to [determine whether] you can get IP chemotherapy. If you are unable to undergo upfront surgery, see if you can get to a center that offers HIPEC.

Practice is changing constantly, and what may be true today may not be true tomorrow. It's a very hopeful era. We have just seen data that the PARP inhibitors can add 3 years in PFS, which is unheard of. What I really want to bring across to patients is that there is hope. There is a lot more research ongoing than what we used to see. I am very optimistic that ovarian cancer will have a much longer survival in the future.