A 59-Year Old Woman With Stage IIIC Ovarian Cancer - Episode 5

Understanding GOG-0218 & ICON7 Trials

Jubilee Brown, MD:In this patient, when I think about bevacizumab and a bevacizumab-containing regimen, is this something that I would do? Well, when I think about this, bevacizumab is almost never the wrong answer. In other words, you wouldn’t use bevacizumab in somebody with massive bowel involvement, and there are a couple of other contraindications. But especially in a patient who is HRD [homologous recombination deficiency]-negative,BRCAwild-type, I think it’s very reasonable to use bevacizumab in patients in the upfront setting during their initial chemotherapy and as maintenance therapy right after. I think that’s always a reasonable option.

I think there are 2 major trials that influence how we practice with upfront bevacizumab use, and of course, these are ICON7 and GOG-0218. GOG-0218 was a cooperative group trial with over 1800 women. They had incompletely resected stage III or IV epithelial ovarian cancer, and they were assigned into 3 groups—1:1:1. Essentially, they received intravenous [IV] carboplatin and paclitaxel, versus that same regimen plus concurrent bevacizumab, versus chemotherapy plus concurrent bevacizumab plus maintenance bevacizumab. That was given for up to 22 cycles afterward.

These patients were evaluated with a median follow-up of almost 103 months, so really good long-term follow-up data on these patients.

GOG-0218, I think the most important finding from this was related to the overall survival that was seen in the group of patients who had stage IV disease. The reason is that we saw a difference in median overall survival, 42.8 months versus 32.6 months. Now, keep in mind that was only for the group who had bevacizumab added to the chemotherapy, so concurrent plus maintenance. That’s important when we administer this; it has to be bevacizumab concurrent with the chemotherapy, with the maintenance therapy to follow. But that I think is really important. The other thing to know is about theBRCAmutation status, and of course those patients do better if they haveBRCA1orBRCA2mutations present.

Now, if we switch over and we think a little bit about ICON7, it was a very similar trial, actually, that evaluated bevacizumab, also a large patient cohort. It was performed in over 250 centers in multiple countries. These patients also had newly diagnosed ovarian cancer, but their regimens were just a little bit different. The patients were given 1:1 therapy with IV carboplatin and paclitaxel every 3 weeks, given concurrently, and continued with 12 cycles of maintenance therapy. That was the plus or minus variable there.

What I think is interesting is that the findings were remarkably similar with ICON7, that we saw poor-prognosis patients do better with this regimen when it incorporated bevacizumab. I think when you put this 2 trials together, it really does inform our practice. That’s where we get the whole recommendation that poor-prognosis patients really benefit the most from incorporation of bevacizumab concurrent, followed by maintenance therapy.

In this patient, when we extrapolate the findings of GOG-0218 and ICON7 and we look at how this patient did, I think we see what happened in both of these trials, that the patient had an excellent response, an excellent response to therapy, as the vast majority of patients do. I’m a little concerned that her CA-125 [cancer antigen 125] didn’t immediately decline to normal, that it was over 35 U/mL at the completion of therapy. But in general, she did have a response that was excellent, as most patients on these trials did.

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