Improving the Management of Advanced Ovarian Cancer

Kathleen Moore, MD:We’ve talked about a historical case, although not that long ago. And then we’ve talked about how decision making has changed and will likely continue to change as new studies emerge this year and next year. Probably one of the more exciting pieces of data to share is an epidemiologic piece of data. That is the fact that despite no change in the incidence of ovarian cancer, and, unfortunately, no change in the mortality, in the United States and in Europe we’re seeing a higher prevalence of ovarian cancer than we’ve ever seen in the past. And so, you might ask yourself, “How is this happening? We haven’t changed how often it’s happening and we’re not changing how often patients are dying, so how do we have more women?” Right now, if I look at what the prevalence is, how are more women with ovarian cancer existing right now than ever in the past? The answer to that is because we have done a great job with maintenance therapies and novel therapeutics and supportive care. So better supportive care, and not with 1 single trial but with successive lines of therapy continually eeking out longer and longer durations of response, stable disease, progression-free survivals. So patients who present to our practices now are often those who have received 3, 4, 5, and 6 lines of chemotherapy and are still, fortunately, well, and are working and want to try new things. This is a very different scenario than I think we’ve experienced in the past. And so, this presents some challenges. While we have a big lineup of chemotherapies that have been in existence and approved for decades, the efficacy of those therapies in later lines is relatively poor. That really hasn’t changed over time.

It’s not that patients are all of a sudden responding to topotecan, because they are not. I am being a little negative about topotecan, but every clinical trial that we have done shows that its response rate is less than 5%. So it’s not that the tumors have changed, but we’re using different drugs.

We have this lineup of chemotherapies that are there, but if you look at those and you look at someone who’s in the fourth line, or beyond, the expected response rate in that population is somewhere between 10% and 15%—response rate meaning when I look at the CT [computed tomography] scan before I treat the patient and I can see some tumor and I can add it up with RECIST [Response Evaluation Criteria in Solid Tumors] measurements. Does that shrink by 30% at any point during their treatment? Ten percent to 15% of the time it does. And those responses, if they occur, are very short lived. So really you may get to maybe 1, or if you’re lucky, the second disease assessment before the patient progresses.

Because we have women living longer and presenting at these later lines of therapy, this truly is a situation of high unmet medical need. We really need to develop therapies that are tolerable. Especially of women I have seen, we’ve seen 3 lines of chemotherapy and you have residual toxicities. What am I going to give you that works, that doesn’t harm you? So tolerable, effective therapies that really provide meaningful prolongation of that progression-free survival. This is a very high unmet need that, fortunately, we’re starting to answer with new drug development.

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