Treatment Options in Stage IIIc Ovarian Cancer

Jubilee Brown, MD:This patient had an upfront surgical debulking, which really for the longest time has been the standard of care. It’s always been our goal to get down to what we call an optimal disease status. There are some important changes that have happened as we’ve learned even more about ovarian cancer and how can treat our patients the best. We know that it’s very important to get down to an R0 [no visible tumor remaining] status. Patients with R0 resections clearly do better than patients who have optimal disease, or where the greatest nodule is 1 cm or less, or patients who have suboptimal disease status. Essentially, whatever we can do to get the patient down to that R0 status is worth doing.

Sometimes we’ll use neoadjuvant chemotherapy in these settings and we have 4 trials now, international trials, suggesting that patients who have neoadjuvant therapy with interval cytoreductive surgery do just as well as patients who have upfront debulkings. The key with this patient is that she really doesn’t have the high-risk criteria that would make her the best candidate for neoadjuvant with interval cytoreductive surgery. In other words, she doesn’t have malignant pleural effusion, she doesn’t have parenchymal liver metastases, she doesn’t have apparent bulky disease that would keep you from getting an R0 resection, and she has a good performance status and can tolerate that upfront surgery.

I agree that in this patient, I would have proceeded with an upfront debulking surgery just like she had. If she had any of those other high-risk issues, if I didn’t think that I could get her down to an R0 resection, or if her performance status couldn’t tolerate a massive surgery, then that I think is the role of neoadjuvant therapy in a patient like this.

When we see patients who have an upfront debulking procedure, patients with an advanced stage IIIc ovarian cancer, the old school way to treat this patient would be straightforward IV [intravenous] paclitaxel and carboplatin. But the field has changed, we have so much more information that helps guide us in how we treat our patients now, that is rarely enough. That’s rarely the right thing to do. When we consider frontline therapy for patients, I think that the first question to ask is, can you debulk the patient appropriately, or are they candidates for neoadjuvant chemotherapy? If they’re candidates for neoadjuvant chemotherapy, then that’s where you would use your IV paclitaxel/carboplatin for 3 to 4  cycles, ahead of surgery.

I think that whether you get down to the optimal disease status with neoadjuvant and interval debulking or, as in this case, with an upfront debulking, then we really guide our treatment based on that germline and somatic testing result. If the patient isBRCA-positive, so do they have a mutation, either germline or somatic, and aBRCAor related mutation or not. Because that’s going to really guide your decision for use of a PARP [poly ADP ribose polymerase] inhibitor versus are you going to use bevacizumab in this patient.

In other words, if she doesn’t have aBRCAmutation, if she doesn’t have a somatic mutation in eitherBRCAor a related mutation, or if she has really widespread disease, so a so-called high-risk patient or poor-prognosis patient, then that’s the patient where I’m going to think about incorporating bevacizumab into her upfront treatment strategy and then carrying it out in terms of maintenance therapy. I think those are the top 2 strategies for determining what I’m going to use.

We know this patient had intravenous and intraperitoneal chemotherapy with bevacizumab, and I will say that I don’t often use that exact strategy. I tend to reserve intraperitoneal therapy for my patients who haveBRCAmutations because when we look at the cohorts in the GOG-0218 and ICON7 trials, it appears that the subgroups of patients who do the best are the patients withBRCA-related mutations. In the absence of that, bevacizumab can usually make up for that difference.

Transcript edited for clarity.

Case: A 59-Year Old Female With Stage IIIC Ovarian Cancer

Initial Presentation

• A 59-year old female presented with new onset early satiety, abdominal bloating and discomfort
• PMH: unremarkable, postmenopausal
• SH: schoolteacher; no tobacco, alcohol or drug use
• PE: abdominal distention, left lower quadrant tender on palpation, shifting dullness noted on percussion

Clinical work-up

• Pelvic exam with transvaginal ultrasound showed a left ovarian mass
• Chest/abdomen/pelvis CT with contrast revealed a left adnexal 4.8-cm mass, extension to liver capsule without parenchymal involvement; retroperitoneal lymph node involvement and ascites noted; no pleural effusion
• Lymph node, adnexal mass biopsy, and paracentesis (2000 cc) cytology confirmed high-grade epithelial ovarian cancer
• Diagnosis: high-grade epithelial ovarian cancer; stage IIIC — T3cN1M0
• Germline/molecular testing showed HRD-,BRCA1/2wild—type
• CA-125, 385 U/mL
• ECOG PS 1

Treatment

• Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
• IP/IV paclitaxel/carboplatin + bevacizumab every 3 weeks for 6 cycles
  • Followed by bevacizumab for 6 more cycles
  • Complete response; post treatment CA—125, 48 U/mL

Follow-up

• 3-months CA-125, 30 U/mL
• Chest/abdomen/pelvis CT showed no gross pelvic masses or nodes
• Pelvic exam, unremarkable
• ECOG PS 0