Dr Chirag A. Shah highlights novel emerging treatments in ovarian cancer and provides advice for community oncologists.
Chirag A. Shah, MD: We have made a lot of progress, but there’s more work to be done in this space. The ongoing research that’s still taking place with drugs that are both approved with FDA fast-tracked designation, and hopefully at some point, we might have some accelerated approvals, are very interesting. The patients with platinum-resistant disease have always been a major difficulty. It’s difficult to go through aggressive surgery, chemotherapy, and then be faced with a short interval to recurrence; it’s crushing for us as providers. Just as the patients are starting to feel better off their treatment, they’re faced with learning that their cancer has recurred. I think immunotherapy has been very interesting because the initial trials for monotherapy for immunotherapy were fairly disappointing. The recent publication of the work at Roswell Park [Comprehensive Cancer Center] was a newer regimen that I’ve found very effective in these patients.
What we know is that ovarian cancers by default tend to be fairly cold. They don’t respond well to immunotherapy by themselves. But I’ve had tremendous success with adding metronomic cyclophosphamide along with Avastin [bevacizumab] combined with pembrolizumab, in the Roswell Park regimen, and the toxicities are actually quite tolerable. I’ve had patients who have had a significantly greater response to therapy and duration of response than they did their platinum-free interval. The recent fast-track designation of approval for nemvaleukin IL-2 [interleukin-2] therapy also in combination with pembrolizumab is very exciting. I think that there’s quite a bit of research also being done in terms of reintroducing sensitivity to PARP inhibitors for patients who progress, whether you reintroduce PARP inhibitor sensitivity by combining it with immunotherapy, or with the newer class of drugs, WEE1 inhibitors.
I think 2022 is going to be a very exciting year in this space; there are several promising research studies being done, some that already have results, and new additional ones. There’s expected to be 8 potential large clinical trials that will have results at various points this year. I think each meeting that we encounter this year is going to bring a plethora of valuable new information. To start with, looking at combinations of immunotherapy to try to make it more active in this space has been very promising. Nemvaleukin IL-2 therapy, looking at WEE1, where those fit, those are really the places where I have the most enthusiasm going forward.
When I look in the state of the science in early 2022, I’d always first suggest if you’re a medical oncologist or a gynecologic oncologist, to engage in discussion on how to treat patients with initial presentation ovarian cancer. I know that myself and my colleagues in our field are very much willing to be active participants in the care of these patients. We have taken a page out of the breast cancer literature in now discovering that in many solid tumors, maintenance therapy, which has really not been a very acceptable or safe way to approach ovarian cancer, should be the standard of care. From my perspective, it’s a paradigm shift. The way I look at it, the only patients who should not receive maintenance therapy are either those who are just not well enough to receive it; for example, you have a patient with a very poor performance status, who’s barely tolerated treatment. You’ve struggled to get her through her chemotherapy, and she’s just unable to do it, or those who just choose not to do it. In my practice, the proportion who choose after the counseling that we’ve had not to have maintenance therapy is very low. I think it’s really a matter of how you frame the discussion. I think back to my early residency days in fellowship, and the biggest problem with ovarian cancer was, it always comes back. You go through all this work, and you get someone in remission, and then lo and behold, it comes back in a time that’s way too short.
We know if we look at all these trials, that the time to recurrence, the median progression-free survival is in the 6- to 8-month range. There are thousands of women who have been studied in these first-line trials at this point, and what we have realized is that time interval that we get until they recur is much shorter than we really would’ve hoped for. Trying to extend that interval, give them more time where they get to be cancer-free, but understanding that some treatment is required to be there; that to me is how we get those prolonged benefits in overall survival. That doubling of the median overall survival in women with ovarian cancer, it’s occurred incrementally. It’s not just been one thing, but it’s getting that extra time in the first line, and then getting some additional time in the second line, and then down the road; that’s really helped us get to where we are. I’d strongly encourage everyone to at least have a discussion. It’s reached the point of being high-level evidence in the NCCN [National Comprehensive Cancer Network] guidelines to offer maintenance therapy to all our patients with first-line ovarian cancer.
Transcript edited for clarity.