Tailoring Treatment Based on BRCA-Mutation Status


Thomas C. Krivak, MD:So the big question is, how should we treat patients with maintenance therapy now? And I think that you’re going to have some practitioners who say we want to watch and wait. You are going to have some practitioners [who] are going to want to use Avastin. The NCCN [National Comprehensive Cancer Network] Guidelines have Avastin as approved as well as poziotinib, as well as olaparib forBRCA-mutation patients, germline or somatic. And again, there [are] numerous clinical trials going on to look at how we may be able to use other agents for maintenance therapy.

How I would look at it is [that] we’re in an era of trying to personalize care. And in looking at the SOLO-1 data, and looking at the Avastin data, [in] GOG-0218 and ICON7, I think it’s really important to offer patients maintenance therapy. We have choices now, and really to look at a molecular target. It would be nice if we had a molecular single for Avastin, say these patients are really going to benefit. We don’t. What we saw is that the high-risk patients have a greater benefit than some of the lower-risk, high-risk-stage patients. But to me, those patients still benefited looking at [GOG-0218] and ICON7.

Going back now and saying, how should we tailor our treatments? To say that somebody [has]BRCA1 or 2unknowns—I think we should investigate that. When you look at the results from SOLO-1, I think when you do that primary debulking surgery or that interval debulking surgery, you can take that patient’s tumor and you can send it off for genetic testing. They test the tumor. In that tumor they should pick up the germline test. If there [are] any germline mutations that should automatically be in the tumor, as well as somatic mutations, and if you would have a genetic alteration inBRCA1orBRCA2, that patient would probably benefit more from being on olaparib.

So I would like to stratify, and I would have to say that since the SOLO-1 data came out, that how we’ve been looking at [them] in our group is, are patients going to get primary debulking surgery or are they going to get neoadjuvant chemotherapy? And some folks in our group want to make sure and test everybody because, again, [those are] the NCCN Guidelines. SGO [Society of Gynecological Oncology], NCCN, [and] ASCO [American Society of Clinical Oncology] all say that any woman with primary peritoneal, ovarian, or fallopian tube cancer should be considered and referred for genetic testing; to me, we have really good genetic counselors, have them get a germline test. But with the SOLO-1 data, if they don’t have a germline, we probably should be testing the tumor as well, looking at some of the survival benefits.

So what we’ve been trying to do is separate out who has aBRCA1[or]BRCA2mutation, use olaparib, or at least offer those patients olaparib, and then the patients [who] don’t have aBRCA1orBRCA2mutation in advanced high-risk disease, go ahead and offer them Avastin. And I think, too, the label for Avastin, I think it’s important that it’s for all comers. We’ve been talking a lot about the high-risk patients, the stage IIIc suboptimals, the stage IIICs [who] didn’t undergo resection in stage IV but really, when you look at debulking surgery, it’s not always just what you finish with debulking surgery that matters. Obviously getting those patients optimally debulked, the patients who require extensive surgical resections, there have been studies that look at if somebody just needs a simpler surgery to get to microscopic disease versus somebody who may require resection of part of their diaphragm, resection of part of the liver, a splenectomy, small-bowel resections, large(?) bowel resections. Those patients are having extensive surgery, and so they have an extensive preoperative disease burden, and to me those patients do have a poor outcome versus patients who have a lower disease burden, and really a lot of folks with ovarian cancer, a lot of patients are going to have that high disease burden. So when you look at the use, that’s clinical how I use it. To me, I use it for all my advance-stage patients. Patients with stage III and stage IV, even when they’re microscopic, to me I think it’s important to give those patients an edge, because some of the patients are going to require extensive surgery to get to microscopic, and I still think that those patients are high-risk.

So I think that when we look at maintenance therapy, I like thinking maintenance therapy for all advanced-stage patients, and then breaking it down into how we’re going to best use Avastin, how we’re best going to use olaparib at this time to try to tease that out. And in about 20% to 25% of patients, you’d expect may have aBRCAmutation. So roughly, you know, 70% to 75% of patients are going to be getting Avastin versus being treated with olaparib.

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


  • 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


  • 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

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