Platinum-Resistant Advanced Ovarian Cancer - Episode 8

Bright Future Ahead for the Treatment of Ovarian Cancer

Thomas C. Krivak, MD:I think it’s time that we start looking at ovarian cancer more as a chronic illness instead of an acute illness. This may sound odd, but you know, [for] somebody who has diabetes, we don’t just give them insulin when they go into diabetic ketoacidosis or have a problem or they start to have end-stage renal disease or vascular disease; they’re constantly getting their insulin. So hypertension, somebody who has hypertension, we don’t wait for them to have a stroke or just repetitive headaches; you’re treating the hypertension. Again, I know cancer is different and chemotherapy is different, but treating [it] as a chronic illness when it’s low volume, using Avastin therapy I think is very important.

Definitely you saw improvement in response rates, you saw it in a doubling of the route response rate in the AURELIA trial in platinum-resistant disease. When you look at Avastin in the OCEANS trial, again, this was a platinum-sensitive cohort; 50% of the patients were responsive to gemcitabine-carboplatin alone when you gave Avastin and improved that response rate up to 75% to 80%. A lot of people believed that some of these clinical trials that have included Avastin in up-front therapy, as well as recurrent setting, were not seeing too much of a difference in the treatment arms because everybody [is] getting Avastin. So bevacizumab or Avastin has been the great equalizer to help improve our response rate or to help improve our PFSs [progresssion-free survivals], and hopefully ultimately to help overall survival.

So using it over the last 10 to 12 years, I think it’s been a great drug. I was a big proponent of it as soon as I saw [GOG-0218] come out as being positive. I thought that was really, really important. GOG-0252 was a combination of an intraperitoneal chemotherapy versus IV [intravenous], versus ID [ifosfamide and doxorubicin] chemotherapy using Avastin. Again, I would treat patients with intraperitoneal chemotherapy, and once it’s completed, then place patients on Avastin. It’s a little bit of a modification of GOG-0252, and we’re waiting for some of the results to get published for that trial.

GOG-0262 showed that Avastin was a great equalizer. And [among] most of the subgroups, patients who got treated with Avastin did well. So to me, I think that the totality of the data [have] showed that this drug is very safe; it’s very effective. There’s no doubt about it that we’re going to have other others, and to me I think that’s the key. When we’re seeing a patient who has advanced-stage disease who’s got a chronic illness, though the cancer may mutate and become resistant, [and] then we want to have options. You know we’re having, like we talked about SOLO-1, the PARP [poly(ADP-ribose) polymerase] inhibitors coming onboard, there may be combinations of PARP inhibitors with Avastin that may improve response rates and prolong these PFSs and Ls. We have immunotherapy coming onboard. So as we have these options for our patients, we’re going to be able to do good because now we have more options—you know, our toolkit has more tools to help kind of fix things as they come along.

So it’s very exciting right now to see some of these combinations with bevacizumab and bevacizumab alone. I can only imagine what’s going to happen later on with some of these other trials, the IMagyn050 trial, which is [a] combination of Avastin with atezo [atezolizumab]. To me, those are going to be very exciting results to see. Because again, we’re talking about patients who may have severe hypertension or develop proteinuria. They may not be able to stand Avastin, so we use a different drug. Or somebody [who] may, we say, hey, we want to use a PARP inhibitor; however, they have toxicity from the PARP inhibitor, and we can come back to Avastin to say, OK, this is going to be the best maintenance therapy for you because you have toxicities due to the other drugs.

So to me, that’s where we’re at. I think that it’s going to show that this is a safe drug, this an effective drug, and we’re going to be able to use it in many different clinical scenarios. I think that’s what makes it exciting at this point.

I think, how I look at it, the changing for ovarian cancer, the stand of care seems like it’s going to be changing very rapidly with the numerous trials that are on the horizon. I mean, there’s a trial looking at olaparib with bevacizumab for patients who do not have a germline mutation. And so, again, it may be looking at do you want bevacizumab alone, do you want a PARP inhibitor alone, or do you want a PARP inhibitor with bevacizumab.

So I think as we get the results of these trials in the next few years, the needle is going to be moving on how we need to treat these, these patients. And you know our research meetings are very important. We have really good clinical trial design. I’m very fortunate to be working in ovarian cancer. And some of these thought leaders, some of these clinical trialists, are just absolutely outstanding with how they’re designing you know just not upfront treatment but up-front as well as recurrent settings in drug development has really taken off. So it’s a very exciting time to be taking care women with ovarian cancer. I really feel like Avastin was the tip of the iceberg and really driving a lot of this change as we’re improving care for women. So I think that’s exciting.

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