Reason for Hope: Moving the Needle on Ovarian Cancer Survival Rates - Deborah Zajchowski

HANNAH LIPPITT:

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Today, Dr. Deborah Zajchowski, scientific director at The Clearity Foundation joins me. The foundation improves the survival and quality of life of women with ovarian cancer across the world. And Deborah is here to talk more about the groundbreaking tools that she's helped develop, so women get access to best possible care, as well as why she's optimistic about the future of ovarian cancer survival rates. Welcome, Dr. Deborah. Could you start by explaining to the audience the story behind how Clearity was founded?

DEBORAH ZAJCHOWSKI: Clearity was founded as a nonprofit organization 13 years ago by a woman named Laura Shawver, who is a PhD scientist, biotech entrepreneur, and an ovarian cancer survivor herself. When she was diagnosed a couple of years before she founded Clearity, she was really shocked that there was just no way to test her tumor to choose her treatment.

At that time, other cancers, like breast and chronic myelogenous leukemia, had drugs that were targeted to proteins that were activated in the tumor because they had specific gene alterations in the tumor. And so you could find patients who had those tumors just by testing the tumors. So she said, why not do the same for ovarian?

And she started Clearity to facilitate access to tests that could help determine each woman's best treatment based on a tumor profile, which today we call precision medicine or biomarker testing. And her hope was that tumor profiles would not only identify the best treatments for each woman, but would also be used to enroll patients for clinical trials, thereby improving the chance of successful drug development.

And indeed, she was right. In 2014, six years after Clearity was launched, Lynparza became the first PARP inhibitor ever approved.

That's a poly ADP ribose polymerase inhibitor for the aficionados. And the trial that led to its approval enrolled only women with inherited BRCA mutations, which are detected by blood tests, because all the science had shown that tumor cells with those kind of mutations were really susceptible to being killed by PARP inhibitors.

So this is a great example of the way that laboratory work can successfully inform a clinical development path for a drug. And there are now three PARP inhibitors approved for ovarian cancer treatment. But the most exciting advances in over 30 years came from the approvals of Lynparza and Zejula at the end of 2018 and early 2019 for maintenance treatment of women who had good responses to first line platinum-based chemotherapy.

In the landmark trial with Lynparza, the women who got this drug have already lived more than three years longer without a recurrence than those who did not get it. And it's looking like there will be more women cured as a result of this treatment.

HANNAH LIPPITT:

That's very exciting news and shows just how far ovarian cancer treatments have come. Now, you've been very involved in creating some of the tools Clearity has to offer, like the tumor profiling report. Could you explain more about this?

DEBORAH ZAJCHOWSKI: I became involved with Clearity at the beginning to help Laura realize her vision.

We identified the appropriate test, created a tumor profiling report for the results, and explained them to patients, in some cases, also to their doctors.

Now fast forward to today, and we no longer need to arrange the tumor testing because it's more routine. But we still try to get the word out about the value of this testing because it's not always performed.

We don't provide medical advice, but we help patients understand their tumor testing results. We provide information about the latest treatment advances on our website and in our discussions with them. And we also help them identify clinical trials that are good matches for their clinical situation, their tumor biology, and personal preferences.

And as Clearity's scientific director I designed and oversaw the development of the tools that we built. And I also oversee a small team of talented people who make sure all of this content is scientifically credible. I also direct our efforts in collaborative research. And we have a data repository that contains the clinical histories and tumor profiling results for over 900 women who have received our services and agreed to have the data used for research purposes. And so we published a number of papers with collaborators using this database.

HANNAH LIPPITT: And how does the report

work?

DEBORAH ZAJCHOWSKI: So each lab provides a report of the test results. And this is where our profiling report comes in because we use that information to generate a more simplified and life friendly display of the results that is in interactive. We show a list of the drugs that are matching the alterations in those genes I just described and others, with links to information explaining why the drugs are matched.

So having tumor biomarker testing is really important because you can provide information that's useful for making decisions about standard drugs, like these PARP inhibitors, or finding other options. And those other options are particularly important if the cancer comes back. These alterations can be detected to match the drugs that are approved in other cancers or maybe only available in clinical trials.

So our report links to those trials is automatically updated, so that you can come back months later and get only the trials that are enrolling at that time.

Everything about this report is web accessible and interactive. So the more you click, the more information you can get.

But we also recognize that there are many promising drugs in trials for which there are no tumor biomarkers that predict likelihood of response.

And in fact, we may even have early clinical data to show that these trials and drugs can be more effective or better tolerated than the treatments used as standard of care. So in order to enable women to find those trials, we built an ovarian cancer specific trial finder on our website.

HANNAH LIPPITT: So here at

Teckro, we highlight the importance of getting early access to trials, both for the physician and the patient. Could you expand on how the clinical trial finder works?

DEBORAH ZAJCHOWSKI: This tool asks a series of questions about the clinical situation, the prior treatments, the platinum response status, genetic and tumor biomarkers, location and other parameters, to find trials for which the patient is most likely to be eligible.

We take the trials directly from clinicaltrials.gov and provide a link back there for more details about the protocol. But our tool saves a lot of time by narrowing down the trial options to only those for which the patients are likely to be eligible and eliminates the time loss and the frustration of going to a trial site and finding out that they're not eligible for those trials.

So we think this time savings for the oncologists is tremendous by using our trial finder. And then there's even a more exciting part of this tool, and that is that we link the trial output from the search to any publicly reported results for the trials or for the drugs that are in the trial.

We even highlight the trials that have reported promising results, so they can be prioritized if there is a long list of options.

And of course, if the user has any questions or wants us to do the search for them, we're here to help on an individual basis with this process. So these tools are what we currently have accessible on the website.

HANNAH LIPPITT: So this is truly game changing when it comes to increasing access. What other factors do you think could help improve trial participation?

DEBORAH ZAJCHOWSKI: As you know, many people have misconceptions about trials. For example, they fear they're going to get a placebo or that they are only supposed to use a trial as a last resort treatment. And I hear these quite often.

So more education is really critical. And there are many groups, including patient advocacy groups, working to provide this.

Another is the extra time it takes to be part of a trial since there are more required visits than to receive standard therapies, and this can be really impractical for many patients. I think one of the learnings from our terrible experience with this COVID-19 pandemic is that virtual visits can work for health care appointments and even for clinical trial check and visits. So this may improve enrollment in the future.

But even with those virtual visits, there's still going to be challenges for patients to enroll in trials if they're too far away.

Hopefully, the movement to open just in time trial sites at the location near where the patient resides will become a reality soon.

There are also racial and socioeconomic disparities that need to be addressed, and many organizations are working on ways to do this. So I'm optimistic that the concerted efforts of pharma and regulatory agents, medical professionals, and advocacy groups will make trials more accessible for everybody in the near future.

HANNAH LIPPITT: What is your prediction of the future of ovarian cancer diagnosis? And what would you most like to see in terms of change?

DEBORAH ZAJCHOWSKI: You know, I think that the greatest impact is going to come from tests to detect ovarian cancer earlier. And there are multiple academic and pharma groups doing this that have shown early signs of promise. So I think we'll see those kinds of tests available in the next five or so years.

On the therapy front, I think we're going to better understand the way that ovarian cancer tumors evade the immune system. And we'll probably have better approaches to ensure that the immune system can recognize and attack tumor cells without being blocked by them. We've made incredible progress in this direction in other cancers and are finally discovering how to do this for ovarian.

There are a number of vaccine, immunostimulatory, immune checkpoint inhibitor strategies that have shown early signs of success in a few patients, especially when they're combined. And we need to know how to match those strategies with each woman and her cancer. So for that, we're going to need to know the biomarkers that predict response.

HANNAH LIPPITT: And

how optimistic are you that the survival rate will increase over the next 5 to 10 years?

DEBORAH ZAJCHOWSKI: I think we have already moved the needle on this one. I think many women who have tumors with BRCA mutations and have been able to get PARP inhibitors will live longer. We should be able to find ways to improve the effectiveness of those drugs for other women and will hopefully translate that into more cures or at least longer lives.

In addition, since many of the drugs being developed now are targeted to patients with specific tumor biomarkers, I can really envision a time when drugs will not be given unless the patient has a good chance to benefit from them. And since such drugs may also be easier to tolerate, women will live longer lives with what may become a chronic disease. Now that said, I hope that in the next 10 years, we're going to no longer need most of these treatments for newly diagnosed patients because the disease is going to be detected much earlier.

HANNAH LIPPITT: Finally, what is the main message you have for those who have recently been diagnosed with ovarian cancer?

DEBORAH ZAJCHOWSKI: There is a lot of reason for hope.

And we at Clearity are here to help you navigate this new terrain.

Our counselors in the Steps Through OC Program can help you manage the fear and the stress that you're experiencing. And my colleagues and I in our treatment decision support program can provide additional information for your discussions about treatment options with your doctor. So please check out our website at clearity.org and feel free to reach out to talk to all of us.

HANNAH LIPPITT: Thank you, Dr. Deborah, for sharing your message of hope with us and explaining more about the incredible tools available to support women and The Clearity Foundation. And that's your dose of Totally Clinical. For all the listeners out there, you can follow Teckro on Twitter.

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