Managing PARP Inhibitor Toxicities and Other Challenges in Community-Based Gynecologic Oncology

Combining a PARP inhibitor with a VEGF inhibitor as maintenance therapy may be an efficacious strategy for patients with advanced ovarian cancer following front-line platinum-based chemotherapy with bevacizumab (Avastin), according to findings from the phase 2 OVARIO study. Still, oncologists in the field have many questions about how to optimize treatment for the patient population.

According to Melissa M. Hardesty, MD, the treatment landscape for advanced ovarian cancer is constantly evolving; however, in the community setting, access issues are being solved more slowly than the science. In Alaska, in particular, oncologists find that their patients travel far distances to receive care. Even with the availability of effective PARP inhibitors, the population of Alaska doesn’t have the same benefit as other patients because managing the toxicity of treatment in the community setting is also a key challenge.

In OVARIO (NCT03326193), patients receiving niraparib (Zejula) in combination with bevacizumab experienced grade 3 thrombocytopenia, anemia, and hypertension at 12 months. The safety profile of the combination was consistent with the toxicity of either drug alone. These are the types of adverse events (AEs) that have been shown to negatively impact patient quality of life.

In an interview with Targeted OncologyTM, Hardesty, a gynecologic oncologist at Alaska Women's Cancer Care, explained the state of gynecologic oncology treatment for rural patients in Alaska and how research is finding answers for improving clinical outcomes.

TARGETED ONCOLOGYTM: How has treatment of gynecologic malignancies evolved in the community setting over the most recent years?

Hardesty: There have been some considerable changes. PARP inhibitors have recently gained regulatory approval for upfront use for maintenance settings, and I think that that's been the most noticeable change in the community for managing ovarian cancer. There's an awful lot more maintenance upfront than there ever was at any point during my training.

It started, of course, with the data regarding mutation carriers. And then last year, it was expanded to all women with ovarian cancer. So, I think that we are now more routinely using maintenance agents after upfront treatment. That would be the most noticeable change in the last year or 2, in the community setting.

What are some of the challenges with treating these cancers in the community setting?

I find challenging in the community setting is dealing with treatment toxicity. There’s an ongoing issue with using maintenance agents because women experience more AEs that persist after upfront therapy. It's a matter of balancing, upfront treatment and maintenance treatment, and the AEs that it has on maintaining quality of life.

We are certainly allowing many women with ovarian cancer to live significantly longer than they have previously. But ultimately, they do end up often suffering recurrences of disease. And when that happens, we want to have them have a good quality of life when they're off therapy or between therapies. I think it's always a balance between toxicity and managing the cancer and trying to allow people to have good quality of life.

Also, in my community, specifically in more rural settings, there's certainly a lot of logistics involved in getting women to care. That often presents some barriers as well.

Population wise, is there anything else unique about modern treatment of these malignancies in Alaska?

First, there are only 2 providers in Alaska that are gynecologic oncologists. Unfortunately, most of our patients do have to do a fair bit of traveling to come to Anchorage to get treated. The only positive thing that's come out of the most recent pandemic is a huge expansion of access of telehealth. That has been wonderful for our patients. We've had a combination of access to telehealth, which has allowed us to treat a lot of women in their community. That's also 1 good thing about the maintenance agents that we're currently using is that they're oral. So, we're able to do a lot more care with a lot less travel.

There's also been a big expansion in supportive care, we have 2 trials open right now that are looking at wellness and weight loss programs that are all done through virtual platforms, and our patients typically would have never had access to things like that. About half of our patients live outside of our main population center. So, most of those patients logistically would just not have been able to participate in these types of programs, and they are now getting access to all of this. It’s been wonderful and has allowed us to improve the quality of life for a lot of our patients in a rural setting.

You gave a presentation related to treating ovarian can in rural Alaska during the

Society of Gynecologic Oncology Annual Meeting this year. What is the key takeaway from your presentation?

It’s important to realize that we have learned a lot about the best ways to manage ovarian cancer recently, and I think we're still learning. As much as possible, we must continue to try to enroll in maintenance trials, even though we have regulatory approval for PARP inhibitors in the upfront setting. There are still a lot going on with regards to finding out if combination maintenance therapy favors certain groups or certain population subtypes. So, as much as possible. We have to put people on trials looking at this to answer our questions.

I presented a non-randomized trial looking at a combination of a PARP inhibitor and a VEGF inhibitor. While the results are certainly favorable, more needs to be learned about for whom that combination is the most effective. All of the maintenance agents do add significant financial toxicity for our patients as well, and I think that it's important for us to use targeted therapy and use them where they're going to be the most effective

We should also continue to learn. I feel like if you asked me what I would advise for a patient, following up upfront therapy a year from now, I may have a different answer. I certainly have a different answer now than I did a year ago. I think that that's going to be a moving target. So, medical oncologists must know there's been a huge shift towards a much more aggressive maintenance strategy, among the gynecologic oncology community. We're going to continue to see that, but I think we're going to continue to need to fine tune it, to figure out for who these agents are best, and which agents are the best, and how to minimize the toxicity, both financial and symptomatic of these therapies so that we can have the best outcomes for our patients.

_Reference:

_{Hardesty MM, Krivak T, Wright GS, et al. Phase 2 OVARIO Study of niraparib + bevacizumab therapy in advanced ovarian cancer following front-line platinum-based chemotherapy with bevacizumab. Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women’s Cancer; March 19-25, 2021; virtual. Abstract 10408}.