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Conference Coverage

Clinical Pathways for Ovarian Cancer

Authored by

JCP Editors


J Clin Pathways. 2018;4(suppl 2):S22-S23.

For ovarian cancer, in which treatment recurrence is a challenge and long-term maintenance therapy is often required, the clinical and financial implications of long-term treatment may differ from those of other treatment settings. This can pose a challenge to using clinical pathways for this disease. Because poly ADP ribose polymerase (PARP) inhibitors have varying indications within treatment for recurrent disease and maintenance settings, and depend on BRCA status and platinum sensitivity, their placement in the pathway may rely on the phase of treatment as well as individual patient factors.

Three speakers at the Clinical Pathways Congress addressed these and other issues relating to clinical pathways use in ovarian cancer.

Thomas Krivak, MD, director of the division of gynecologic oncology, Allegheny Health Network, Women and Children Institute and the AHN Cancer Institute; Pittsburgh, PA 

Why is pathways development for ovarian cancer particularly challenging?

I think ovarian pathway development is a challenge because when you see a patient with ovarian cancer, different doctors are going to have multiple ways of looking at that patient. There is plenty of data out there to support various treatments for patients with ovarian cancer. If you use upfront treatment of a newly diagnosed ovarian cancer patient as an example, people would agree that they need a platinum taxane-based treatment and they need surgery. The FDA just approved bevacizumab for maintenance, but some patients may get that while others may not, because, when you looked at other clinical trials, certain dosing of other drugs may alleviate the need for maintenance treatment with bevacizumab. So there is a small number of patients and a lot of data that supports numerous ways to treat—the science is definitely there, but the art of medicine is trying to apply that science to each patient. We all view our patients slightly differently. It is a definite challenge to say there is a true winner in some of these treatment plans, because it can be greatly debated.

How are PARP inhibitors beginning to be integrated into clinical pathways in the maintenance and recurrent disease settings?

I think PARP inhibitors are one of the most important developments that we have had in recent years for ovarian cancer. When I was a fellow back in the late 1990s, early 2000s, a lot of medical oncologists were not doing any kind of maintenance therapy up front, or for recurrent. But now, we have had 3 PARP inhibitors come on the market really quickly—a fourth and a fifth probably to follow—and it is going to take us awhile to exactly figure out which PARP to use for each patient. The PARP inhibitors are going to have different side-effect profiles and different dosing, so figuring out which PARP to use for which patient is going to be a challenge. In light of this, pathways should incorporate numerous PARPs and not just say one PARP as your only choice, because there are those different side-effect profiles.

For anyone who has a recurrent platinum-sensitive ovarian cancer, the data is very strong that those patients should be treated with platinum therapy, and those that respond should receive a PARP inhibitor. To me, with 3 or 4 large, randomized, phase 3 trials all showing a benefit for patients being treated with a maintenance PARP, that is something that should be incorporated into the guidelines fairly quickly. What exact PARP inhibitor it is, I think that the physicians and patients should be given an opportunity to choose between them.

To accommodate all of the new data that is coming out in ovarian cancer, how often, in your opinion, should pathways be re-evaluated and potentially updated?

I think they need to be reevaluated every 3 to 6 months. Again, we just had SOLO-1 that was presented in Germany, which is some of the most remarkable data that we have seen in upfront ovarian cancer and needs to be reflected in recommendations. Then off the top of my head, I think there are an additional four to five phase-3 clinical trials that are going to be reported soon, probably in 2019, that may change standards as well, and there are going to be two in the recurrent setting.

Overall, there are going to be numerous drugs, and drug development is fairly rapid right now for many cancers, with ovarian cancers definitely being one of them. Clinical pathways are going to have to be looked at quite frequently. On the other hand, leaving pathways broad and allowing more physician discretion may mean they do not have to be updated quite as often.

Dr Krivak presented at an Innovation Theatre entitled “Considerations for ZEJULA Maintenance Treatment in Ovarian Cancer,” sponsored by Tesaro Inc.

Susana M. Campos, MD, MPH, assistant professor of medicine, Harvard Medical School; Dana-Farber Cancer Institute; Boston, MA

What are some of the unique considerations for using clinical pathways in ovarian cancer?

Ovarian cancer can be a bit challenging simply because the disease is complicated. If it presents at an advanced stage, it is actually a very heterogenous disease, and you could have multiple histologies. Patients will relapse at different times. You will have the platinum-sensitive group of individuals, and you will have the platinum-resistant group. You have to be mindful of what category these patients will eventually fall into. There are times when it is very difficult to tell when a patient is platinum-sensitive or platinum-resistant.

Also, while there are many drugs available for ovarian cancer, how you navigate those drugs is extremely important. By putting one drug before another, you actually expand the options that are available to women with ovarian cancer. You have to be very cognizant of: Where is the patient’s disease? How is the disease playing itself out? What is the patient’s age? How do you navigate the care?

At the end of the day, you have to present the individual with as many options that are available as possible.

How are PARP inhibitors beginning to be integrated into pathways for ovarian cancer? Is it happening in the maintenance setting, recurrent setting, or anywhere else along the care continuum?

Absolutely. In the maintenance setting, if a patient is platinum-sensitive, has recurrent disease, responds to a platinum doublet (regardless of which one the clinician chooses), and has a BRCA mutation, then she is offered a PARP inhibitor. Even if the patient does not have a BRCA mutation, we do offer a PARP inhibitor. As you know, the NOVA study, the SOLO-2 study, the STUDY-19, and the ARIEL3 study show that all patients, regardless of germline mutation or somatic mutation, had a benefit to a PARP inhibitor. In turn, we do offer all women with platinum-sensitive recurrent disease a PARP inhibitor.

What are the key considerations that Dana-Farber weighs in ovarian cancer clinical pathways? Do evidence, guidelines, FDA approvals, or other factors carry the most weight?

The answer to that question is largely clinical data. Everyone is very familiar with the data at hand, whether it be the upfront data, the recurrent data, platinum-sensitive data, or platinum-resistant data. We know our own patient population, so all of that factors in to how we navigate clinical trials. Our pathways are all based on published data.

Dr Campos presented an educational session entitled “Evaluating Clinical Pathways for Ovarian Cancer Treatment and Maintenance Therapy.” This educational activity was supported by educational grants from AstraZeneca and Tesaro, Inc.

Dana Chase, MD, FACOG, Arizona Oncology-The US Oncology Network

What are the most recent notable developments in the treatment of ovarian cancer?

PARP inhibitors have begun to work their way into clinical pathways for both maintenance and treatment for recurrent ovarian cancer. Currently, we are counseling patients regarding these medications and using them frequently in practice. They will continue to play a role in the treatment of ovarian cancer. Many of our open clinical trials are using these drugs in combination with other standard and experimental agents.

Which setting in ovarian cancer is most in need of more research?

Platinum resistant recurrent ovarian cancer is definitely an unmet need with limited options. In addition the rarer ovarian cancers such as clear cell ovarian cancer, low grade ovarian cancer, and ovarian carcinosarcoma are all areas of greatly needed novel therapeutic approaches. PARP inhibitors have limited utility in these settings thus far.

What are the key considerations that Arizona Oncology weigh in determining ovarian cancer clinical pathways? 

Arizona Oncology currently does not mandate ordering regimens through pathways programs; however, National Comprehensive Cancer Network clinical practice guidelines and FDA-approved indications are most likely to guide insurance approval. This then affects the ability for the practice to provide a patient with a certain treatment regimen.

Dr Chase presented at an Innovation Theatre entitled “Rubraca (rucaparib) Tablets for Treatment or Maintenance Treatment of Recuurent Ovarian Cancer,” sponsored by Clovis Oncology, Inc.

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