Treatment Approaches for Ovarian Cancer

Thomas Herzog, MD:So, I think the first decision that you need to make is, is she a candidate for interval cytoreduction? And I’ve talked about some of the things that one considers there. Having made that decision to not do that and discussing it with the patient in terms of what the relative pros and cons would be, as well as the anticipated benefit, you then move to systemic treatment. We have multiple options today. As our audience probably knows, bevacizumab has been recently approved for platinum-sensitive disease. This is an opportunity here to use this. There are several things that make me interested in using bevacizumab, and one of the primary things is that she has ascites and she’s symptomatic from that. So, you have multiple options in terms of what one could do. Most people would certainly use a platinum at this point, being that it is platinum-sensitive disease, and it would be considered to be highly platinum-sensitive being that the time interval is almost 2 years out for her.

When you pair something with platinum, you have multiple choices. There’s literature looking at paclitaxel and there’s also literature looking at pegylated liposomal doxorubicin, as well as gemcitabine. If you bring bevacizumab into the mix, there have been 2 phase III trials that have looked at the use of incorporating bevacizumab in platinum-sensitive patients. The first one is G0G213, which is also interesting because you had a surgical component with this trial, so it was basically a bi-factorial design where you make a decision if the patient is a candidate for surgery or not. And if they are, they then get randomized to surgery or not. Then, you have the decision as to whether they would go on bevacizumab along with the carboplatin/paclitaxel backed up. And so, this is a fairly large trial, with the endpoint of overall survival that showed an advantage for those patients who were treated with the bevacizumab until progression.

You also have a second phase III trial where platinum was paired with gemcitabine plus or minus bevacizumab. And I think, again, it was a little bit different in the construct of the trial in that the primary endpoint for this trial was progression-free survival; about a 4-month advantage in progression-free survival with a hazard ratio that was 0.46. So, it was a very good response that was seen. The other thing that’s really important when you look at these patients and are trying to figure out whether you want to incorporate bevacizumab or not is the actual response rate. This lady comes back into your office and she’s symptomatic. That’s a patient in whom you really do want to see an objective response rather quickly. This is a lady who is going to be calling you about her inability to eat, and if she is, there could be problems further on from here. She could have an impending bowel obstruction down the road. Fortunately, she did not have any signs of that, which would be important in terms of making her a candidate for bevacizumab.

I think it’s important to look at that because the data from both of these phase III trials show a significantly higher response rate if bevacizumab is added. It’s about 78% if you have bevacizumab and it’s about 56% or so if you don’t have bevacizumab. So, you significantly increase the response rate, which is something that’s important in a patient with this profile. The other thing to consider is herBRCAstatus because that gets into the potential spectrum of choices at this point as well. Knowing herBRCAstatus would also be important with the new approvals of PARP inhibitors.

The platinum-free interval is very important in terms of predicting how a patient is likely to respond to a platinum-based therapy. And so, what we’ve really done is we’ve broken patients up into those that fail within 6 months of having received platinum, and we characterize those patients as being platinum-resistant. If it’s more than 6 months, they’re considered to be platinum-sensitive. Now, many people will subdivide the platinum-sensitive patients into those that recur between 6 and 12 months and call those intermediately platinum-sensitive, or partially platinum-sensitive, and then classify those who recur after 12 months as highly platinum-sensitive. So, again, it’s a spectrum. And one needs to recognize that if someone’s 6 months and a day out, they’re probably not going to behave all that much differently than someone who’s platinum-resistant versus someone who recurs, as in this patient, almost 2 years out and is likely to be highly platinum-sensitive. And the prognosis that is associated with that platinum-free interval is very strong. So, the further out you go, it’s a continuous variable. The chances of responding become greater.

Transcript edited for clarity.

May 2015

• A 56-year-old woman presented to her gynecologist with urinary frequency and persistent abdominal bloating. The patient reports maintaining normal activities and a moderate exercise.
  • PMH: Hypertension, well-controlled or spironolactone
  • Abdominal ultrasound showed a complex mass in the right pelvis measuring 4.5 X 5.0 X 7.5 cm
  • Physical exam: fluid wave test positive for ascites
  • CA-125, 622 U/ml
• She was referred to a gynecologic oncologist for further evaluation.
• CT of the pelvis and abdomen showed a right complex pelvic mass, ascites, and omental cake. No other peritoneal lesions were visualized.
• Based on CT findings, she was scheduled for surgery.
• The patient underwent complete resection with no residual disease remaining.
• Diagnosis, epithelial ovarian cancer, stage IIIC
• She received 6 cycles of carboplatin every 3 weeks (AUC 6) and weekly paclitaxel (80 mg/m²) for 18 weeks.
• Follow up labs showed normalization of CA-125 to less than 10 U/ml

April 2017

• Almost 2 years later, the patient reported having symptoms of persistent abdominal distention and weight loss. She reports feeling tired and napping during the day.
  • CA-125 level, 330 U/ml
  • CT scan showed peritoneal seeding consistent with carcinomatosis
• Diagnosis: platinum-sensitive recurrent ovarian cancer
• The patient was started on bevacizumab (15 mg/kg) plus 6 cycles of carboplatin (AUC 5) and paclitaxel (175 mg/m²) every 3 weeks with a plan for bevacizumab maintenance therapy.
• After 2 cycles of therapy, she developed grade 2 hypertension (156/94 mm Hg); this was subsequently controlled by adding an ACE inhibitor to her diuretic.
• The patient has continued therapy without incident.