Case 1: Use of Maintenance Therapy in Ovarian Cancer

Thomas C. Krivak, MD: Case 1 continues here. Germline molecular testing was BRCA wild type, and the patient was homologous recombination deficient [HRD]. My assumption is this is based off the Myriad myChoice test. The patient had high-grade epithelial ovarian cancer involving the omentum, both ovaries, and metastatic disease to the lymph nodes.

What are the current treatments available for this patient, for primary up-front therapy? We can get into a nice discussion on this. This patient is optimally debulked for microscopic disease, she’s young, she’s fit, and she’s HRD positive, or homologous recombination deficient. A platinum-based chemotherapy regimen is important. I try to do IP [intraperitoneal] chemotherapy for the young patients who desire to be treated as aggressively as possible. There’s a role for IP chemotherapy in this patient, a population that does have increased [adverse] effects with abdominal pain, nausea, and vomiting. The IP cisplatin at times does have some chronic renal, I see some changes with baseline creatinine. This patient will get some type of platinum-based chemotherapy. I like IP/IV [intravenous] chemotherapy for them, but she can also be treated with platinum-based carboplatin and paclitaxel. I’m curious to see what my colleagues think about this.

Shannon Westin, MD: Chad, what would you do?

Chad Hamilton, MD: This patient is HRD positive, BRCA wild type, right?

Thomas C. Krivak, MD: Correct.

Chad Hamilton, MD: According to the NCCN [National Comprehensive Cancer Network] Guidelines, the preferred regimens would either be the every-3-weeks carboplatin–Taxol [paclitaxel] regimen or perhaps CARBO-Taxol-bevacizumab [carboplatin-paclitaxel-bevacizumab], with bevacizumab maintenance. Specifically in this case with the optimally debulked patient, then the IV/IP certainly comes back into play. To be honest with you, I’ve waffled on where I stand on IV/IP; a lot of our specialty has. I can’t say I’m consistent in what I do at this time with these patients. Some of it depends on performance status and intangible things that go along with that. I’m probably doing more every-3-weeks [treatment] at this point than IV/IP, but either is certainly a reasonable option.

Shannon Westin, MD: I agree with Tom regarding how we do our testing. We’ve generally done germline testing first and then done a reflex to somatic and HRD if the germline is negative. For this patient, the presence of HRD-positive disease is going to sway me and might sway me more to just chemotherapy only versus doing, say, chemotherapy with bevacizumab or whatnot. I know this patient has been optimally debulked, and I’m going to be able to get her onto subsequent PARP inhibitor maintenance. My goal is to get a good response to therapy and then transition her to maintenance.

I use less IP therapy since the results of GOG-0262 and ICON8. I was doing a ton of dose-downs, I was doing IP, and then everything seemed to be a wash, and it seemed that chemotherapy every 3 weeks was fine. My practice has changed to some degree. That being said, in a young woman that I’ve gotten down to no gross residual disease, I talk to them about intraperitoneal therapy. To your point, the intangibles, some of it is where they are located, can they get IP therapy where they are, and is it safe? If it is, then I encourage them to consider that. For other characteristics that help me make a decision, the performance status of the patient: do they have to work, what are their other responsibilities? All those things have to influence it.

Chad Hamilton, MD: In contrast to your testing scheme, we are sending our patients pretty early after their diagnosis, 1 of their initial visits, to our genetic counsel like you are. Almost in parallel, we’ve been ordering somatic testing of some sort on those patients. Some patients get lost between our office and trying to get to the genetic counselor, so I don’t get that information back quickly. They will drag their feet, life will intervene, or they will get overwhelmed with everything. I find it a lot more helpful if I get the ball rolling, which we can do on our end, for the somatic testing. That should capture about 95% of folks who will have a germline mutation as well. It’s a catchall if patients don’t move forward with getting their germline testing done.

Thomas C. Krivak, MD: Germline testing is important for 2 reasons: treatment but also cascade testing. An ounce of prevention is better than a pound of cure. I like the panel test because that identifies some other low-penetrance genes that may have an impact. I’ve been doing this long enough that I’ve treated patients and now have seen family members and done risk-reducing surgery. That makes me feel good that people are following with the genesis, and they are talking with their families and getting that done. I completely agree with Shannon in that I like using IV/IP chemotherapy, but your focus was on making sure people stay healthy enough for maintenance. My biggest concern at times is this: if I harm them or make them sick, they don’t want maintenance off IV/IP. It is probably more important to make sure those patients are doing well coming off their adjuvant chemotherapy to go on maintenance. That is 1 concern that our utilization of IV/IP chemotherapy has decreased. Very nice.

Chad Hamilton, MD: Your last question was how this scenario influences your decision to add bevacizumab to the treatment regimen. As Shannon mentioned, the HRD aspect sways me to think more about PARP maintenance. I am still reserving bevacizumab for those patients who have bulky residual disease or a lot of ascites, the ones that we really had a signal in the subgroup analysis of the phase 3 trials who may be getting more bang for their buck from the bevacizumab maintenance.

Shannon Westin, MD: I agree with that. My decision to use bevacizumab is based on those factors rather than anything else. For this particular patient who we’ve been able to get to an R0, I likely would not use it.

Thomas C Krivak, MD: I’m a big bevacizumab proponent. It’s the volume of disease before surgery is important. Even if they get to R0, I’ll still use it. It’s a struggle because it meets with the label, but you see the data and you understand the data. That’s a bias where some of the science supports me not using it, but my bias has been to use it because intuitively, I think it works in that patient population.

Shannon Westin, MD: Now you have the opportunity that you can add PARP for this patient, let’s say, with an HRD-positive tumor. If you’ve started bevacizumab, then you don’t have to make the decision of whether you want to keep going with the bevacizumab or stop it. You have data to support using both.

Transcript edited for clarity.