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ASCO 2019 Interview- Ovarian Cancer- Robert Coleman

Robert Coleman, MD, FACOG, FACS

Professor, Vice Chair of Clinical Research, and the Ann Rife Cox Chair in Gynecology

Department of Gynecologic Oncology and Reproductive Medicine

Executive Director, Cancer Network Research

The University of Texas MD Anderson Cancer Center

Houston, TX

Ovarian Cancer: Past, Present, and Future

Ovarian cancer, for many years and currently, is really thought of as a rare tumor. We see just north of 20,000 new cases a year, and the number of new cases, the incident cases, and the number of deaths that are due to this disease have been relatively unchanged, and really have not inflected very much. In fact, if anything, there is probably just a slight downward trend in the new cases. But we’ve seen survivorship start to increase in the last 20 years or so. That survival rate has gone from percentages in the mid-thirties to now almost 50%, so there has been some improvement in the median survivorship at five years.

But what’s really impressive with this disease is what we call the prevalence; the number of patients that actually have the disease at any one time. That number has escalated dramatically just in the last 10 years, going from around 170,000 or 175,000 cases in 2005 to about 230,000 cases in 2016. This dramatic increase in prevalence is a reflection of the impact of different therapies that are now starting to reach the clinic, especially in the last couple of years. There have probably been two major components to that: the introduction of PARP inhibitors, and the introduction and more widespread use of angiogenesis inhibition.

When we started thinking about where this impact has taken place, from 2014 until just currently, we’ve seen 12 new indications in GYN cancers in general, and nine new indications in ovarian cancer, three of which surround the angiogenesis inhibition. Bevacizumab now is an indication in frontline concomitantly with chemotherapy and primary maintenance, platinum-sensitive recurrence in combination with chemotherapy and secondary maintenance, and in treatment of patients with platinum-resistant disease. And then of course, the PARP inhibitors enjoy approvals both as treatment and as maintenance therapies; the most recent of these being Olaparib, which gained approval in December of last year, and just gained approval for primary maintenance among patients with BRCA mutations. So, there has been a tremendous upsurge in new approvals and broadening of indications.

Addressing Challenges and Unmet Needs in Ovarian Cancer

I think most people who treat this disease recognize that the greatest challenge that we have is that we still diagnose patients in advanced stage disease: so, our inability to identify an early stage precursor, set of symptoms, or biomarker that would identify those patients that would be diagnosed with diseases limited to the pelvis, or even in the preinvasive state. That’s our real critical unmet need. And it’s also the kind of characteristic that would really change the paradigm of this disease, and its expectations for survivorship. But I do think that the good news/bad news about new drugs is that there are more available, but they are also now being used earlier and earlier. And so, what we traditionally used to treat patients with recurrent disease were these novel agents, and these agents are now going to be administered to patients earlier and earlier in therapy, leaving the recurrent space full of patients who have previously been exposed to these drugs.

We’ve made a lot of great progress, but on the other hand, the question is, what are we doing next? I tell people to try to be really thoughtful, and to tease through the data very carefully, about who they give these drugs to. Right now, there’s a large number of trials ongoing that are adding even a third agent into treatment. They are adding this third agent either concomitantly with chemotherapy, or in maintenance immune checkpoint inhibitors, which have generally not been very successful as single agents, and only limited activity, even as combinations in patients with ovarian cancer. But now they’re being incorporated into frontline trials, where they’re being used with chemotherapy in combination with angiogenesis inhibition and maintenance, even as triplets, with all three drugs being given at once. So again, we’re kind of in a situation where we’re using the drugs a bit indiscriminately, which challenges us when it comes time to start counseling patients for recurrence regimens as well.

On the Horizon in Ovarian Cancer

There are number of seminal things that are going to happen this year. The first is that we anticipate the publication of the randomized trial, which was looking at the role of secondary cytoreductive in patients with platinum-sensitive recurrent disease. We presented this at ASCO last year. We anticipate that this will be in print this year, and it shows that patients who have that characteristic actually do just as well with chemotherapy and no surgery as they do with surgery. So that will lead to a lot of discussion.

The next major thing that will happen in about six months, after the ESMO meeting, is that we will have data for several phase-three trials that are looking at the role of PARP inhibitors and other drugs in patients with ovarian cancer. We expect to see a trial looking at Olaparib given in combination with chemotherapy and primary maintenance. We will also have the PAOLA-1 trial, which will be looking at the role of Bevacizumab and Olaparib as a maintenance strategy.

We also expect to see the GOG-218, which looks at the role of MEK inhibitors in patients with low-grade serous ovarian cancer; that phase-three trial will be presented there. And finally, we expect to see the data from the PRIMA trial, which looks at Niraparib, in patients with homologous recombination deficiency, as a maintenance strategy: the same space where Olaparib is currently approved for patients with BRCA mutations.

That is just a taste of what’s going to happen in the next year. Over coming years, we will evaluate patients to see who are the best candidates for these classes of drugs. We expect to see some expansion of the antibody drug conjugates. Then, I think, the biggest next change will probably be evaluating patients who’ve had prior exposure to these drugs, and what works in combination. There are a number of trials which are maturing now, that are looking at those new combinations.

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