Selecting Optimal Upfront Therapy for Ovarian Cancer

Robert L. Coleman, MD:Options for therapy in a patient like this who, first of all, has metastatic disease and had an optimal debulking essentially range around IV chemotherapy. Now, this particular patient actually received intraperitoneal chemotherapy. We have a series of trials, phase III, that have demonstrated that intraperitoneal chemotherapy led to an improvement in progression-free and overall survival. And so, we feel that the intraperitoneal route has some merit.

I will say that there has been decline in the use of intraperitoneal therapy, particularly as we’ve gone on and modified the regimen to make it more tolerable. One of the major issues we saw in the phase III work we did with intraperitoneal chemotherapy was that patients had some toxicity, and some of that toxicity was related to the dose and the administration of the drug; a result of catheter-related side effects; or maybe related to poor management of the GI side effects. All those caused us to actually modify the regimen. The big question that comes up then is if we modify the regimen, can we expect the same survival benefit?

That has been the focus of new and ongoing trials that have been done. Most recently, GOG-0252 was a trial that looked at IP therapy, intraperitoneal therapy, in a dose-dense or weekly administration of therapy versus standard Q3 weekly therapy that was given in combination with bevacizumab. Interestingly, in that group of patients that this patient would have been eligible for, they saw no difference between any of those arms. And so, I think that many clinicians now on the cusp of potentially seeing bevacizumab approved in the frontline setting have started to think about this a little differently. Although treatment standards may still include intraperitoneal therapy, I think many of us are looking at the intravenous route with that kind of combination.

Intraperitoneal chemotherapy has largely been focused around patients with a small volume of residual disease. I think the thought was that if we put chemotherapy in the belly, it will then coat the surfaces where the tumor lives in the small-volume and smaller-volume disease and we would expect to see not only this direct surface penetration in the tumor, but also—because that gets absorbed—it go intravenously in through the vascular systems and actually get to the tumor from the vascular route. That was the hypothesis. I think as I mentioned with GOG-0252, there may be less of a measurable value for that specific approach if we use this other intravenous strategy, particularly if bevacizumab, which is an antibody against vascular endothelial growth factor, is available to us. We’ll have a decision in the near future about that.

The residual disease can be one of those decision points as to whether or not you would use IV or IP from the standpoint of therapy. In the past, we have said that if a patient presents with residual disease that’s more than a centimeter, we would go the IV route. Based on data that were initially developed through the Japanese GOG trials, it looked as though the dose-dense regimen of paclitaxel would have been the best of those options.

More recent data have suggested now that dose-dense rate in the European population may not have much of an effect. I think people now are actually reverting back to where we were back in 1996 when paclitaxel was approved, and that’s using it on a Q3 weekly basis with carboplatin across all disease cohorts. I think there’s still some controversy about this, and we’re still sorting out the details. I do think that some of the more recent large phase III trials would suggest that intravenous route, even in patients with bulky disease or small-volume disease, along with bevacizumab would still be an acceptable treatment regimen.

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