Expanding Role of PARP Inhibitors in Advanced Ovarian Cancer - Episode 5
Transcript: Ursula A. Matulonis, MD: Most of our women who come in with a new diagnosis of ovarian cancer do have advanced disease, meaning they have evidence that the cancer has left the ovaries and has gone into the upper part of the abdomen or lymph nodes within the abdomen, meaning stage III, or stage IV, when the cancer leaves the abdominal cavity and goes into a lymph node in the neck, under the arm, or in the groin. So over 70% to 75% of women who are diagnosed with ovarian cancer have advanced-stage disease, so stage III or stage IV.
Regarding the management of these women who come in, I really consider their status as almost a medical emergency because a lot of folks will come in with a lot of symptoms and significant symptom burden of abdominal pain, abdominal swelling, or difficulty eating. They may have shortness of breath, either because their cancer is pushing up against the diaphragm, causing them not to be able to take deep breaths. Or sometimes they have liquid around the lungs and you can actually find cancer cells in the pleural effusions. Those are related to the cancer. Sometimes patients can even have pulmonary emboli, so blood clots in the lungs because of the advanced nature of the cancer and really because ovarian cancer can be prothrombotic.
It’s really important that patients be seen very quickly in a tertiary cancer center where they have access to gynecologic-oncology surgeons, medical oncologists—I’m a medical oncologist, and I treat women with ovarian cancer—genetic counselors, sometimes nutritionists, and pathologists who are expert in gynecologic pathologies, specifically ovarian pathology. And that the team assembles, and the primary decision maker here is the gynecologic-oncology surgeon. So the gynecologic-oncology surgeon makes that determination if the patient should go to surgery first—meaning she goes to cytoreductive or debulking surgery first. Or the decision to not go to surgery but do a biopsy of the most easily accessible site of solid tumor—not just simply ascites removal but biopsy in the omentum and peritoneal mass—and make the diagnosis that way quickly. And then once a diagnosis is made, starting chemotherapy with carboplatin and paclitaxel.
The chemotherapy also certainly has undergone some changes over time where a few years ago, we were using more weekly paclitaxel in addition to once-every-3-week carboplatin. And a trial called ICON8 has really showed us that once-every-3-week carboplatin-paclitaxel appears equivalent to carboplatin and weekly paclitaxel or weekly carboplatin and weekly paclitaxel.
Kathleen Moore, MD: The recommended approach for a woman who presents with advanced ovarian cancer is really to be very thorough and individualize your treatment plan to that particular patient. There’s not a 1-size-fits-all answer to this question. It is a combination usually of surgery—and that surgery is called a cytoreductive surgery—and chemotherapy, and the chemotherapy is a combination of 2 very well-tolerated drugs, 1 is carboplatin and 1 is a taxane. Most commonly it’s paclitaxel, but it could also be docetaxel for example.
And so how you sequence those 2 has been the focus of several large clinical trials where they’ve randomized patients with advanced disease to a chemotherapy; or to a surgery first, followed by chemotherapy; or to something called the neoadjuvant approach, where you give chemotherapy first, 3 or 4 cycles, then do an interval surgery called an interval cytoreduction followed by additional chemotherapy.
And the endpoints for most of those trials were both progression-free and overall survival. So there’s been this argument about whether or not to do that operating and debulking on everything you could see, really ideally to the point that you can’t see any cancer when you’re done. There are still cells there, but you can’t see it. And then giving chemotherapy removes as many of the resistant clones as possible. So you’re just mopping up the rest with the chemotherapy as opposed to starting with a lot of chemotherapy. Giving chemotherapy gets a nice response too, because ovarian cancer is very chemotherapy sensitive. But you’re also sort of preselecting your resistant clones, so it sets the patient up theoretically for a shorter progression-free survival.
And so there were several studies that were done that didn’t really demonstrate a difference. Very consistently in all 4 of the studies that have reported, there was no difference in progression-free survival and overall survival between the 2 approaches.
Now, there have been a lot of criticisms of those studies regarding the patient selection. Proponents of frontline surgery really feel like the patients who were selected for the trial were those who the physician weren’t passionate about operating on either way, as opposed to people you looked at on the CT [computed tomography] scan and you said, “Oh, I can get all that out for sure.” They feel like those patients didn’t go on the trial.
So there are also questions about the amount of effort that went into the surgery on those studies, even though there are 4 and they’re very consistent to map and met with universal acceptance of the findings. And why that is important to keep discussing is that if there is indeed improvement in progression-free or overall survival with frontline surgery, then we ought to be doing that, and patients ought to be seeing highly qualified surgeons who can do that surgery.
If there really isn’t a benefit, then it’s safer to give chemotherapy first and then do the surgery in the middle because the surgery is not anywhere near as radical as it is when you do it before chemotherapy.
This is still an important question. So for the patients who could go to the OR [operating room], it’s really up to patient and physician discussion—shared decision making. For patients who present with disease that’s clearly just not gettable, with lots of cancer in the liver, for example, or disease in the lungs—not just pleural effusions; pleural effusions we still operate on but not actual disease in the lungs. Those patients really always start with chemotherapy and then get a surgery in the middle. And then there’s a population of patients who just never get surgery. It’s a small population, but they’re just never good candidates, so that’s a group as well. We don’t really plan to not do surgery.
Transcript Edited for Clarity.