Questions Remain Across Treatment Modalities in Ovarian Cancer

John Comerci, Jr, MD

The emergence of PARP inhibitors in ovarian cancer treatment has led to a prolonged survival benefit without sacrificing quality of life (QoL), said John Comerci, Jr, MD. However, several questions still exist related to surgery, neoadjuvant chemotherapy, and immunotherapy.

“The introduction of the PARP inhibitors [into the paradigm] is probably the most significant advance that I've seen in my 30-year career,” said Comerci. “Everyone has a story of women with recurrent BRCA-positive disease who are started on PARP inhibitors and truly get a really significant increase in progression-free survival (PFS). They also maintain a really great QoL.”

Beyond the advances seen with PARP inhibitors such as olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula), progress has also been made in determining which patients are candidates for upfront surgery. Factors such as age, comorbidities, performance status, and physiology, among others, can be used to inform selection for this approach, he added.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Comerci, associate professor, Department of Obstetrics, Gynecology & Reproductive Sciences, and vice chair, Women's Health Line Specialty Services and Referral Physician Relations, University of Pittsburgh Medical Center, provided an overview of advances made in ovarian cancer and remaining challenges to address with future research.

OncLive: Beyond PARP inhibitors, where has the greatest progress been made in ovarian cancer?

Comerci: We've really come a long way in the past 10 years or so in terms of deciding which patients are surgical candidates out of the gate, as opposed to patients who [should] receive neoadjuvant chemotherapy. Our goal as oncologists should be to provide patients with the most impactful therapy, but one that does not really impact their QoL. We've really come leaps and bounds in determining which patients are good candidates for upfront surgery versus those who are not. We have been able to—particularly with older patients, women are living much longer, into their 80s and 90s—offer those patients aggressive therapy. Most of those patients are not going to have upfront surgery based on their age, comorbidities, and performance status.

What are some other factors to consider when selecting patients for surgery?

You have to look at what the patient brings to the table. You have to look at their support systems. There are some 80-year-old patients who are physiologically 60 years old, while there are some 80-year-old patients who are truly 80 years old in terms of their ability to perform activities of daily living. I always tell my patients that, “Debulking surgery is equivalent to [running] a 5K in terms of the physiologic stress that it puts on the body”—that is number one. Number two, you need to look at their imaging. We've been using laparoscopy more in terms of trying to determine in which patients it makes sense to proceed with a debulking. I believe that all of those [factors] come into play.

Could you expand on how you’re using laparoscopy in your institution?

Most of us would start out by putting a scope in anyone who has a good bit of disease burden on a CT scan. Sometimes if you look at a CT scan, and you have a large pelvic mass and a straightforward omental cake and not a lot of what appears to be small bowel mesenteric involvement or diaphragmatic involvement, you can maybe skip laparoscopic examination. However, in anyone else, I believe it's a benefit. The patient avoids a big incision, we’re able to get them in and out of the hospital, and [we can] start chemotherapy much more quickly.

What are some of the key unanswered questions that need to be addressed?

The question of intraperitoneal (IP) chemotherapy is very user-dependent. There are some people who really feel that it offers patients an advantage based on GOG-172, and there are others who do not feel as wedded to that idea. Do you use IP chemotherapy in the patient who received neoadjuvant chemotherapy? Do you put a port in after you treat them initially? Do you chemically debulk them and then physically debulk them? With the debulking, do you put a port in and treat them? Many of us do it, but I don't believe there are much data out there to support that one way or the other.

Other questions have to do with when to introduce a PARP inhibitor. Do we use a PARP inhibitor as second-line treatment or is it truly maintenance therapy? How long do we use them for as a maintenance therapy? Those are other questions that I believe are important.

Where do you see future research headed?

[A lot of work is being done with] personalized medicine and really looking at the tumor itself and trying to understand, from a molecular standpoint, what it's susceptible to. I honestly believe that is where we're headed. Treating [patients with] ovarian cancer is like trying to swat a fly with a hammer. However, I believe that as time goes on, we're going to be examining each patient's tumor individually and deciding on the best way to treat those patients.