Platinum-Resistant Advanced Ovarian Cancer - Episode 4

Frontline VEGF Inhibition in Advanced Ovarian Cancer

Thomas C. Krivak, MD:For this patient, front-line bevacizumab therapy, I think, is very important because she has multiple high-risk features. She’s got the ascites. She had a high CA 125. She had stage IV disease, and she sub-optimally debulked. To me this is a patient who’s [highly] likely to recur. You know my belief is that there’s definitely a role for maintenance therapy in this patient. Again, some practitioners don’t, and I can understand that. However, to me, with her presentation, she’s high risk. If you look at ICON7, that was the study that looked at high-risk patients—stage III, suboptimal stage III without any resection, and stage IV—and you really got an improvement in their overall survival [OS] of about 9 to 10 months in ICON7 for that high-risk group.

Unfortunately, when you look at the high-risk group in the other groups, you know that the survival was probably a difference by about 15 to 20 months. So to me, the high-risk group, unfortunately [is] at risk for recurrence and usually [doesn’t] have as good as overall survival. So to me, I would have placed the patient on Avastin up front.

I think that we have accumulating evidence that Avastin is safe using bevacizumab as maintenance therapy up front, and then you can use bevacizumab as maintenance therapy for patients who have platinum-sensitive recurrence as well as platinum-resistant recurrence. And so to me, I think that over the past decade to 15 years, we’ve seen numerous studies that have really shown the safety as well as efficacy of Avastin or bevacizumab in many lines of treatment for these patients. And again, you’re seeing not a decrement in quality of life with the addition of bevacizumab, and you’re seeing, I think, better control of symptoms as well as improving your overall response rates in many clinical situations.

I think the rationale for anti, you know, vascular agents or bevacizumab is pretty straightforward. Ovarian cancer, ascites is very well controlled by Avastin. You know VEGF, which is what Avastin blocks, was [a] vascular permeability factor at 1 point. So to me, patients who have ovarian cancer at times can have very high VEGF levels. So trying to disrupt those levels, trying to block those levels, makes a lot of clinical intuition. And, well, getting down into how it may work at the endothelial level—as well as, you know, structuring blood vessels, destroying blood vessels, allowing better tumor penetration with chemotherapy. I think there are a lot of many basic science aspects of this drug that make it very enticing to use in patients who are a high risk for relapse.

The rationale for using Avastin or bevacizumab up front as maintenance therapies, when you look at ICON7, you look at GOG-0218. GOG-0218 had a PFS [progression-free survival] improvement of about 6 months, I think, in the final analysis. The overall survival wasn’t different, so the patients or practitioners say there was no difference in overall survival. I can understand how they’d say that. However, there probably was a lot of crossover. And what I mean by that is patients who didn’t receive bevacizumab at the time for maintenance probably received it in a later course of treatment.

So these patients are getting this drug, so there can be some contamination of the overall survival data. But there was an improvement in PFS of about 6 months. And then when you look at ICON7—again that was the companion European study—and you look at the high-risk group, to me, that high-risk group really benefited from the use of bevacizumab as maintenance therapy.

So when you look at the totality of the data utilizing maintenance bevacizumab and you look at up-front ovarian cancer, the two large clinical trials that were run in 2018 in ICON7, and you look at the OCEANS trial, you look at AURELIA, you look at GOG-0213, all those trials that were designed for a PFS endpoint or over, they were meeting their endpoints, and you’re seeing an improvement in either the PFS or the OS. And so to me, having all that totality, the data, as well as the safety, as well as the ease of administration and low [adverse] effects, to me I think it makes an ideal drug. It’s like any drug that we do in development, when we were first starting and having some phase II trials, there was concern about spontaneous bowel perforations.

And again, with Avastin there [are] black box warnings if you have recurrent remissions for small bowel obstructions, or if you have a lot of disease on the rectosigmoid colon, you shouldn’t use this drug because those patients are at high risk. So it’s like anything in medicine, as we develop these new drugs and as we learn how to use them, I think we’re being able to use these drugs more efficiently, more safely, and getting more clinical benefit as we [become] used to using Avastin for the treatment of ovarian cancer.

But to me I think there [have] been numerous studies all showing a benefit. And again, some of it progressive-free survival, some of it overall survival. And again, the safety data that [show] that it is, to me, is a very well-tolerated drug for our patients with up-front ovarian cancer.

Transcript edited for clarity.


Case: A 70-Year-Old Woman Presenting With Advanced Ovarian Cancer

H & P:

  • A 70-year-old woman presents for evaluation of left-ovary mass discovered during a recent pelvic exam. She reports abdominal tenderness, urinary symptoms, and a “bloated” or “full” feeling, despite normal diet and bowel movements
  • Postmenopausal, no children
  • PE: reveals a woman of low normal weight (BMI = 19 kg/m2) with hypertension; abdomen is distended and shows dullness to percussion
    • BP = 135/80 mm Hg on metoprolol
    • Fasting glucose = 95 mg/dL
    • LDL = 90 mg/dL

Imaging

  • CT with contrast of pelvis, abdomen, and chest reveals multiple peritoneal lesions and spread to outside of liver
  • Malignant ascites present

Biopsy and labs:

  • Pathology: high-grade epithelioid adenosarcoma, ovarian primary
  • BRCA1/2status: unknown
  • CA-125: 656 U/mL

Treatment

  • She underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and tumor debulking; residual disease after cytoreduction: 1.25 cm
  • Diagnosis: stage IV ovarian cancer, grade 3
  • Started on carboplatin and paclitaxel plus bevacizumab; achieved a partial response
  • She was continued on maintenance bevacizumab

Follow up:

  • Follow up imaging at 6 months showed disease progression in the liver
  • She was started on paclitaxel plus bevacizumab