Approaching Platinum-Refractory Recurrent Ovarian Cancer

Robert L. Coleman, MD:This patient has an unfortunate situation with a relatively short recurrence-free interval. I mentioned in the earlier part of this that we had treated her with intraperitoneal therapy. The likelihood that she would have a recurrence at 4 months following that therapy and that surgery is actually quite low. So, the biology of this cancer is already starting to demonstrate that it actually has some growth factors that are falling outside of the norm. And to be honest with you, we’re still trying to figure out exactly what it is that drives a tumor like that that’s not falling into what are normal expectations.

But having said that, we have a patient who has visible measurable disease within a 4-month window of completing what looks to be very good therapy. And I think that should tell you something about what’s going on with the biology. If you think about how long it takes a mass to actually present itself as measurable in a 4-month window, it almost has to be present at the completion of chemotherapy from the last cycle. And she just finished platinum-based therapy.

So, one of the questions that always comes to me in a patient like this with a short recurrence interval is, how do we tell the difference between platinum resistant and platinum refractory?

This is a patient though that actually although she has no persistent disease at the completion of primary therapy, which would be kind of the standard definition of refractory, I kind of lump her in with that same group. Because she actually has measurable disease within a 4-month window, which, to me, would suggest that the tumor actually essentially was present but not visible at the completion of her frontline tumor.

So, having said that, we see that she underwent an evaluation. And many times, for patients like this, we would actually go for a biopsy to understand any somatic alterations that could happen in this particular tumor. That might be an important kind of aspect to add to the clinical scenario for decision making. But at this point in terms of our approaches, we would establish the diagnosis and then plan for treatment.

The question I frequently get is, “Can we cut it out? Can we go back to surgery?” And it’s not an unreasonable request from patients because they had that when they had their very first procedure that they underwent when they were addressing their initial diagnosis. And it’s a good question. I also get this from a lot of referring physicians who are not surgeons. So, gynecologic oncologists would recognize that this is a common question that comes for a patient with this kind of recurrence.

What I would say is, unfortunately, surgery doesn’t work in a vacuum. Patients who are chemoresistant—and this would be a scenario where the patient has recurrence within a 4-month window, or even within a 6-month window—their disease is already manifesting a degree of chemoresistance. In that situation, it appears that surgery would probably not be of great benefit. Because if you can imagine, if you’re able to remove all the disease in a chemoresistant situation, you can’t just not treat. So, there needs to be something to be given in addition to the surgery. And if they’re already resistant, that tumor will just grow back. And in some respects, it can grow back even faster because of the amount of cytokines, the chemicals that are released in the healing process of undergoing surgery.

So, we would think that from the standpoint of who’s the best patient to operate, I think we’re still trying to sort that out. But fortunately, we have 3 randomized prospective studies in patients who have chemosensitive disease where they are randomizing patients, women, with this recurrent disease to either surgery or no surgery followed by chemotherapy. And we should have some information about this on the outcome of overall survival very soon, and I hope to share that in an upcoming review.

Transcript edited for clarity.

December 2016

• A 38-year old female presented with bloating and pain
• PMH: unremarkable
• FH: no malignancy
• Abdominal/pelvic CT scan: pelvic mass (9-cm) arising from the right ovary, omental cake (15-cm), and extensive peritoneal carcinomatosis
• CA-125: 1027 U/mL
• The patient was diagnosed with stage IIIC epithelial ovarian cancer
• She underwent hysterectomy, bilateral salpingo-oophorectomy, and omentectomy
  • Scattered residual peritoneal nodules (<1 cm) remained following surgery
• Following surgery, treated with 6 cycles of IP/IV carboplatin/paclitaxel
  • After 6 cycles of therapy, CA-125 level declined to 2.5 U/mL
  • Symptoms were ameliorated

March 2017

• Patient reported bloating and abdominal pain
• Lab results showed elevated CA 125 (985 U/mL)
• CT scan confirmed recurrence with ascites and visible disease (2-cm peritoneal mass)
• She was treated with bevacizumab and topotecan for 4 cycles
  • Patient had good response therapy
  • After 4 cycles, she was switched to bevacizumab maintenance

October 2017

• Patient returned with complaint of abdominal pain
• CT scan revealed ascites and several 1- to 2-cm peritoneal masses in the pelvis and upper abdomen