Managing Recurrent Advanced Ovarian Cancer in the Current Era

Kathleen Moore, MD:I just presented the case of a patient who was diagnosed many years ago and is still, fortunately, doing well. Fortunately for us, things have changed. Standards of care have changed and we have developed new therapies, and how we think about treatments has evolved. We can start in the frontline setting.

For patients who are diagnosed now with advanced ovarian cancer, one of the first things we want to know is whether that patient has either a mutation in herBRCAgene that she was born with, which is called a germline mutation, or whether she has a mutation in her tumor, in thatBRCAmutation. In a patient who does not have a germline mutation…when we think about high-grade serous ovarian cancer, which is the most common type, about 18% of patients are going to have a germlineBRCAmutation, or what we refer to as aBRCA-associated cancer.

But if that testing is negative and you test the tumor, you will find about another 7% of patients who have what’s called a somatic mutation in their tumor. And so, it’s incredibly important that we identify those patients as early as possible. Certainly, once we have the diagnosis confirmed and the patient has recovered from surgery, if that was the chosen path, we really want to get this testing sent because it does impact how the patient is treated in the frontline setting.

It doesn’t impact the choice of chemotherapy. That has remained the same, with doublet chemotherapy, carboplatin and paclitaxel, still being the standard of care with or without bevacizumab. That is a new finding as well, or a new indication for patients with advanced disease. They can have bevacizumab added to the frontline, and then after a response, continued for about 15 cycles. So that’s 1 option.

But for patients with aBRCA-associated tumor, or a mutation in the tumor, somatic disease, the new standard of care is chemotherapy with a response, which is very common—about 80% of patients have a response—followed by the PARP [poly ADP ribose polymerase] inhibitor, olaparib, maintenance therapy until progression, or until the 2-year mark has been met. And at 2 years, if the patient is still ongoing on olaparib without progression, the treatment is discontinued, and close monitoring ensues from there.

There are 2 changes there that I just talked about. The olaparib indication is a result of the study called SOLO-1, which was presented in 2018 and has really led, very rapidly, to global approvals. They’re still ongoing because of unprecedented improvements in progression-free survival in this particular population of women who have aBRCA-associated cancer. The progression-free survival for the group that received placebo was right around 13.8 months. For those patients who received olaparib, again, just for 2 years, the median progression-free survival in the study wasn’t yet reached but is estimated to be around 49 months. The hazard ratio there was 0.3, so a 70% reduction in the risk of progression. So again, unprecedented results—the order of magnitude of which we have never seen in ovarian cancer. And so it is the standard of care in that population.

Bevacizumab was also approved in the frontline since our patient was initially managed. That is based on what’s called the Gynecologic Oncology Group [GOG] 218 study in the United States. ICON7, which was a European study, was not exactly the same but was very similar. They enrolled patients, giving them bevacizumab with chemotherapy, as compared to placebo, and placebo maintenance, and demonstrated a statistically significant improvement in progression-free survival with an improvement in the hazard ratio for progression as well. Not as robust as what was seen in a biomarker-directed study, like SOLO-1, but still an improvement in progression-free survival.

And so, the decision now when you have a new patient with ovarian cancer is, what do you do? What do you start with? Do you start with a bevacizumab-based regimen with the chance that you’re going to discontinue the bevacizumab if the patient has aBRCA-associated cancer because you’re going to put her on olaparib to follow? Or, do you wait for the genetic and genomic testing and then make that decision? There’s not an easy answer to that question, but those are the treatment decisions that we’re having to grapple with right now in the front line.

Transcript edited for clarity.

Case: A 58-Year-Old Female With Heavily Pretreated Recurrent Ovarian Cancer

H & P

• 58-year-old female diagnosed in 2014 with stage IV ovarian cancer
  • Pathology: high-grade serous carcinoma, epithelial ovarian cancer
  • CA-125: 460 U/mL
  • CT with contrast of the pelvis, abdomen, and chest revealed a 4-cm mass in the left ovary and peritoneal carcinomatosis
  • Patient underwent suboptimal debulking surgery; residual disease 1.5 cm
  • Received IV/IP carboplatin/paclitaxel (6 cycles); achieved complete remission
• 2 years later (2016) symptoms returned; CA 125, 255 U/mL; ECOG: 1
  • Received carboplatin/paclitaxel (6 cycles) and bevacizumab; achieved good partial remission; CA 125, 45 U/mL; continued on bevacizumab maintenance
• 1.5-years following second-line therapy (2017), again presented with symptoms; CA 125, 550 U/mL; ECOG: 0
  • Genetic testing;gBRCA1/2wild-type
  • Received carboplatin/gemcitabine (6 cycles); CA 125, 46 U/mL; achieved complete remission
• Currently:
  • CA 125, 620 U/mL
  • CT shows several small masses in the lung left lower lobe (largest is 3 cm)
  • ECOG: 0