Report Back from SGO: What’s the Latest in Ovarian Cancer?

00:00:00:00 – 00:00:36:01
Unknown
Today’s webinar report back from studio. What’s the latest in ovarian cancer? I’m Maggie Nicholas Alexander, the senior director of Gynecologic Cancer Patient Support and Education at Share. Today’s webinar, we’ll focus on any new information and research advances from the Society of Gynecologic Oncology annual meeting held in March before the presentation begins. I’d like to tell you a little bit about share.

00:00:36:03 – 00:01:12:20
Unknown
SHARE is a national nonprofit that supports, educates and empowers anyone diagnosed with breast or gynecologic cancer and provides outreach to the general public about signs and symptoms because no one should have to face breast, ovarian, uterine, cervical or metastatic breast cancer alone. For more information about our upcoming webinars, support groups and helplines, please visit our website at sharecancersupport.org

00:01:12:22 – 00:01:46:24
Unknown
This webinar is being put on in partnership with the National Ovarian Cancer Coalition, and since 1991, the NCC has provided support to thousands of cancer survivors, delivered millions of educational resources, and connected with countless local community partners to raise awareness about ovarian cancer. You can learn more about all that they offer on their Web site at ovarian talk.

00:01:47:01 – 00:02:19:15
Unknown
Now, I’m going to go over some housekeeping items. All participants will be muted during the presentation. Once Dr. PEREIRA finishes presenting, we’ll begin the Q&A discussion. Feel free to ask questions through the Q&A section at the bottom of your screen. Remember that, Dr. PEREIRA cannot give specific medical advice, so please keep your questions, General. We also have closed captioning available.

00:02:19:17 – 00:02:51:10
Unknown
You can enable this feature by clicking the live transcript button at the bottom of the screen and selecting the subtitle option. This webinar is being recorded and will be available on the share website soon. We’re very excited to have Dr. PEREIRA joining us as today’s speaker. Thank you so much for being here. And now I’ll hand it over to you, Dr. PEREIRA, to introduce yourself.

00:02:51:12 – 00:03:09:17
Unknown
Hi, I’m Dr. PEREIRA. I’m a dual oncologist at Lenox Hill Hospital located in Manhattan, New York, and I’ve been practicing there for close to seven years. It’s kind of hard to believe time goes by so quickly. I did most of my training in New York City. I have an interest in doing research, and most of my research is in cervical cancer.

00:03:09:17 – 00:03:36:10
Unknown
But we also have opened phase one trials in our practice for ovarian cancers as well. And I’m very excited to be here. Thank you for having me. And I guess we’ll begin the presentation. Sounds good. Thank you. Go ahead and share. And so today we will be talking about what’s the latest in ovarian cancer, a report back from ASCO.

00:03:36:12 – 00:03:59:03
Unknown
I think it’s important to see kind of where we are, how far we’ve come in order to understand where we’re going when it comes to the treatment of ovarian cancer. And so, as many of you know, ovarian and fallopian tube cancers are the second most common GI malignancy with an incidence of about 26,000 patients annually in the U.S. affecting one in 70 women.

00:03:59:05 – 00:04:25:02
Unknown
And most of these are epithelial ovarian cancers, which make up 90% of the malignant ovarian tumors. Management through management throughout is typically consisting of a combination of surgery and chemotherapy, with or without targeted treatments. And we’ll talk a little bit about how those targeted treatments are kind of such a new part of how we manage these ovarian cancers.

00:04:25:04 – 00:04:54:15
Unknown
And so the combination of carboplatin and paclitaxel is currently the standard backbone of treatment, and none of that has changed. Even with the new data that came out of SGA this year. This is because 70% of women with advanced ovarian cancer will achieve a complete clinical remission after initial surgery and platinum based chemotherapy. And so this combination is both effect of and has a generally manageable toxicity profile for patients with certain inherited mutations.

00:04:54:15 – 00:05:16:13
Unknown
Targeted therapy, such as PARP inhibitors can significantly improve outcome. And we’ll talk a little bit about those as well. And so I just want to spend a few minutes on the basic science of chemotherapy. And I think it’s important to understand how chemotherapy works in order to fully appreciate what it means or what makes the newer therapies more targeted.

00:05:16:15 – 00:05:36:15
Unknown
And so the cell cycle is represented here at the circle represents the active part of the cell cycle. So the part of the cell cycle that’s involved in cell growth and division G0, which is kind of popped out to the side of that circle, represents when when cells are at rest, when they’re not dividing, when they’re not growing.

00:05:36:17 – 00:06:04:04
Unknown
And so rapidly dividing cells such as cancer are constantly in the active phase of that of the cell cycle. And chemotherapy works by targeting different aspects of the cell cycle. The idea is that cancer cells are more sensitive to chemotherapy than the normal cells. And since our bodies also have normal cells in the active phase, such as hair and bone marrow, this can lead to the off target side effects that we’re all familiar with for chemotherapy.

00:06:04:06 – 00:06:32:17
Unknown
And chemotherapy is all we had for a really long time. It wasn’t until 2011 that we started adding more targeted therapies to the Carbo Taxol backbone. And this slide is kind of busy on purpose because I think it nicely highlights just how many studies and how many FDA approvals occurred over that subsequent decade. And if you zoom in on the different trials, you’ll see that all of these are either a PARP inhibitor or bevacizumab.

00:06:32:19 – 00:07:05:22
Unknown
And so I thought we should talk about exactly what makes those two drug classes targeted just over the next two slides. And so bevacizumab essentially binds to the circulating vegetable, which interferes with the endothelial cell proliferation and blocks new blood vessel formation. So generally fast growing tumors will quickly outgrow their blood supply. So they have a mechanism for up regulating the way that they can recruit new blood vessels.

00:07:05:22 – 00:07:43:00
Unknown
So they continue to grow, essentially bevacizumab to block the ability for tumors, to make new blood vessels. And so it slows or stops tumor growth in that way because the tumor cells specifically have these receptors increased or upregulated. The treatment specifically targets the cancer cells leading to fewer off target side effects than you would typically see. For example, in chemotherapy, have inhibitors are another interesting target therapy for some patients.

00:07:43:02 – 00:08:06:19
Unknown
As many of you know, I’m sure ovarian cancer is driven by certain gene mutations commonly referred to as either Brassica or hardy mutations. Basically, cells have several ways of repairing the mistakes that can be made during cell division. Cancer cells with the bracket mutation are missing One of these mechanisms, so they rely on the park pathway for DNA repair.

00:08:06:21 – 00:08:28:14
Unknown
If you block PARP, those cells cannot repair the DNA mistakes and this triggers a signal for the cell to die. This is a targeted treatment because the normal male cells and non-cancer cells in the body still have working bracket. So if you block PARP in those cells, they have the other repair mechanism and so those cells won’t die.

00:08:28:14 – 00:08:56:01
Unknown
And it focuses. It targets really just the cancer cells specifically. Before we dive into what’s new from. So I think it’s important for us to kind of review and understand how do you want oncologists look at these studies and how we determine which new treatments can be beneficial to our patients? There are a few different ways that we define success in a clinical trial.

00:08:56:03 – 00:09:22:03
Unknown
Progression free survival is the most common primary outcome in Phase three trials and the definition of progression free survival is time from completion of treatment to recurrence. And this can be expressed in months as median progression free survival, meaning the time it takes 50% of patients to recur, or as a percentage of patients who have not recurred at a specific time point.

00:09:22:05 – 00:09:49:22
Unknown
And so some trials, for example, report their progression free survival at three years. They just they have enough data and they want to get it out there. And so they’ll report the percentage of patients who recur at three years in each arm rather than waiting for 50% of patients to recur. Overall survival. The definition is similar, but instead of time from completion of treatment to recurrence, it’s time from completion of treatment to death from disease.

00:09:49:24 – 00:10:16:00
Unknown
And this can again be expressed in months as median overall survival or as a percentage of patients on a specific time point hazard ratio is another really important endpoint. It’s expressed as a decimal and gives an indication of how much better or worse the experimental arm is. I think out of all of the the different outcome data, in many ways this one’s the most helpful.

00:10:16:02 – 00:10:48:17
Unknown
So, for example, a hazard ratio of 0.6 means that patients on the experimental drug are 40% less less likely to have their cancer return and an h R of 1.4 would mean that a patient on the experimental drug is 40% more likely to have their cancer returned. With the experimental drug going of all of the trials that we review, especially when we look more closely at the trials that were reported earlier this year, You’ll see a combination of these different outcomes reported when comparing the experimental drugs to the standard treatment.

00:10:48:19 – 00:11:15:15
Unknown
And and so very briefly and I spend some time on this is really kind of a zoom in on that busy slide that I showed you a few slides ago. The slide highlights the outcome advantage seen with added targeted therapies, the Carbo taxol arm. And so all of these trials just added targeted therapy to the carboplatin paclitaxel regimen That continues to be the standard of care.

00:11:15:17 – 00:12:06:12
Unknown
And so the prima and sola trials are two PARP inhibitor trials. And I just wanted to really show this slide because the progression free survival advantage with the addition of PARP inhibitors to chemotherapy is so profound. And in some trials you gain up to a year and in some trials, you know, almost two years of a progression free survival advantage by adding a PARP inhibitor to patients with the BRAC mutation and earlier trials looked at adding bevacizumab at to carbo taxol and showed approximately a four month progression free survival advantage to adding Avastin and the duty to 18 within the US icon seven was done in Europe slightly different outcomes but still shows improvement in

00:12:06:17 – 00:12:46:11
Unknown
progression free survival treatment at time recurrence. Very similar regimens. Here again we’re looking at PARP inhibitor maintenance and the and bevacizumab maintenance one added to chemotherapy in the recurrent setting. So now for the main event, this year’s meeting was held in San Diego and there were several really exciting ovarian cancer trials discussed at the meeting this year. The first one is a maintenance study looking at the addition of another PARP inhibitor to the Carbo Taxol Backbone.

00:12:46:13 – 00:13:19:04
Unknown
This is referred to as the Athena Mono study. We’ll talk about why it’s called the mono study in a second. But essentially, patients with newly diagnosed stage three and four ovarian cancer were included. And this was in the front mindset. So patients were included if they completed the platinum doublet. So that carbo platinum paclitaxel and had surgery and they had to have demonstrated a complete response and that they were sensitive to the chemotherapy.

00:13:19:06 – 00:13:44:24
Unknown
As is often the case with the design of these trials, patients had to have a good performance status and no prior lines of treatment because again, this was FRONTLINE, the trials called a four arm study. And basically the model part of the trial is looking at just two of the arms and the combo trial is looking at the other two arms.

00:13:45:01 – 00:14:14:09
Unknown
And and so what’s interesting about this study is that the combo arm actually also includes a an immunotherapy drug. Whether or not immunotherapy can be helpful in cases of ovarian cancer is still an area of the ongoing research. And so the combo and the Monroe trials kind of happened. At the same time. The results from the managed trial matured more quickly and the combo data is not available yet.

00:14:14:11 – 00:14:55:24
Unknown
Hopefully that will come out soon because we were all eager to to find out if we can start using immunotherapy in ovarian cancer and similar ways that we’ve used it in our other GYN cancers. And so patients were randomized to receive either Rucaparib or a placebo and the maintenance treatment would continue for up to 24 months. And what it means for it to be a maintenance trial is that patients get the upfront six cycles of the carbon taxol and then the Rucaparib and the PARP inhibitor in this case is continued for up to two years.

00:14:56:01 – 00:15:21:19
Unknown
This data was previously published. This is not what was presented at issue this year, but of course I think it’s important. So I’m going to spend a little bit of time on it. And so one of the ways that we look at progression free survival in these trials is with a kaplan-meier curve. And so basically monitoring events over time and as kind of a quick cheat, if the lines are so divergent that you can fit your thumb between them.

00:15:21:19 – 00:15:52:21
Unknown
And that’s usually a clinically and statistically significant difference. And so you can see the blue line, which is the recap, red and the red line, which is the placebo, those lines are pretty far apart. And so at quick glance you can see that the Rucaparib has quite a benefit over placebo in preventing recurrence. That dotted line that goes straight across from 50 that represents that median progression free survival that I mentioned earlier.

00:15:52:23 – 00:16:28:12
Unknown
And you can see that at 36 months. So at three years, the Rucaparib arm had not even met that median progression free survival, meaning that fewer than 50% of patients recurred at three years. These are amazing results. And the hazard ratio you can see listed just below those numbers, the hazard ratio of 0.4. In this case, that means that if patients were on the recall arm, they were 60% less likely to recur for their cancer to recur.

00:16:28:14 – 00:16:57:22
Unknown
What’s interesting about this PARP trial is that it included both positive and negative patients. And out of all the trials that have done this, I think this showed the most positive results in Nebraska negative arm. So basically showing our copper that can be a benefit to patients who don’t have one of those mutations. The BRAC and negative data is on the bottom part of this graph and you can see a hazard ratio of 0.58.

00:16:57:22 – 00:17:26:22
Unknown
So that 0.6. And so patients, even if they were negative, were 40% less likely to have recurrence of their disease if they were in the experimental arm. So these are really, really important results and very great data. And so what was presented at ASCO this year was the more long term follow up. And so the like I mentioned earlier in the talk, the primary end point in a lot of these studies is progression free survival.

00:17:26:22 – 00:17:53:04
Unknown
But there are other end points that are also quite meaningful. And so the follow up, the long term follow up data that was presented was the time to first subsequent therapy and the progression free survival to the PFC two. PFC two is basically for patients who recur, who then go on a subsequent chemotherapy regimen. How long is their second progression free survival?

00:17:53:06 – 00:18:21:19
Unknown
And then another one of the end points in this case, the secondary endpoint. They also reported on overall survival this year. And so the first the first slide looks at the time to first subsequent treatment. And I think the results from this are a little bit intuitive. If it takes a patient longer to recur, I think it’s intuitive that it would take them longer to go on another chemotherapy regimen.

00:18:21:21 – 00:18:48:02
Unknown
And so I didn’t find these results to be too surprising. But it did show that patients who are on the PARP inhibitor had a longer interval between needing another chemotherapy regimen, the PFC two. So again, how long was the second progression free survival after subsequent chemotherapy? This slide shows that there isn’t much difference between the copper rib and the placebo arm.

00:18:48:05 – 00:19:23:18
Unknown
And the reason that’s important is because one of the questions we always ask ourselves when we’re looking at new therapeutics is, is this drug going to somehow make the tumor or the cancer less or less responsive, less sensitive to the chemotherapy is ever already using? Will it creates some resistance in the tumor. And so, you know, when you don’t see a difference in the PFC two, it’s basically showing that being on a PARP inhibitor doesn’t create additional resistance to subsequent chemotherapy lines.

00:19:23:20 – 00:20:12:21
Unknown
Kind of giving another metrics to say that this is a safe and effective treatment. They reported an overall survival. Overall survival always takes longer to mature. And so a lot of times overall survival will not be included in the initial publications. And so the overall survival was reported at the meeting this year. I think in general, when oncologists find overall survival to be a difficult end point, to make sense of it with ovarian cancer, especially when analyzing first line treatment, because patients, once they come off of the trial, they can receive any combination of the of regimens surgeries.

00:20:12:23 – 00:20:41:22
Unknown
It’s such a mixed bag that I think the overall survival gets a little bit diluted. And this trial did not show a difference in overall survival. But how meaningful that is is really it’s hard to say. Based on all of this data. Rucaparib became approved for maintenance in the upfront setting for both patients with the BRAF mutation and without the mutation in Europe.

00:20:41:24 – 00:21:21:22
Unknown
And that approval has not happened through the FDA yet. But I understand that it’s being applied for. And so shifting gears a little bit to another clinical trial that I think is one of the more exciting things that has come on the scene in ovarian cancer treatment in the last few years. And this is patient reported outcome results from the Phase three Mirasol trial looking at more of a Tex Mab threat to seen versus investigator’s choice of chemotherapy in patients with folate receptor positive platinum resistant ovarian cancer.

00:21:21:24 – 00:21:44:12
Unknown
What is more of a tux? Some abstract and seen also referred to as Merv, which is I think what I’ll start calling it for the rest of this talk, because the rest is kind of a mouthful. Merv is an antibody drug, a conjugate that targets the full weight receptor alpha. So these these protein receptors live on live on normal cells.

00:21:44:12 – 00:22:17:14
Unknown
But in case of ovarian cancer, there is an upregulation sort of an abundance of these folate receptors. Although ovarian cancer cells have a lot of these folate receptors, a fuller receptor itself doesn’t drive the cancer. So it by itself is not a target. So what they’ve done is create these antibody drug conjugates where they have design an antibody that will interact with the folate receptor and then attached chemotherapy to it.

00:22:17:16 – 00:22:49:21
Unknown
So this ADC, this antibody drug conjugate, this ADC comes along, it attaches to the cell, the cell brings it inside and the chemotherapy can be released and target the the cell directly. And so I think of all of the new or drug types, this is one of the most exciting, this trial. And the next trial that I’m going to review are both this type of a drug activity.

00:22:49:23 – 00:23:19:11
Unknown
And so the Mirasol study, the results of the outcome data was also previously reported. And the the data reporting issue this year was just patient reporting outcomes. But I think, of course the cancer specific outcomes are also really important. So I’m going to spend some time presenting those two. And so just to discuss the trial design, again, we already discussed that this was for patients who had platinum resistant disease.

00:23:19:11 – 00:23:50:12
Unknown
The definition of platinum resistant disease is a progression free survival of less than six months. The folate receptor or alpha had to be detected on pathology with special stains and had to be upregulated in over 75% of tumor cells. Only high grade serous histology was included and patients had to have received 1 to 3 prior lines of therapy.

00:23:50:14 – 00:24:32:17
Unknown
Prior Avastin sorry, prior bevacizumab and prior PARP inhibitors were allowed in. Patients with bracken mutations were also allowed, and so patients were randomized to either receive the treatment or receive investigators choice of single agent chemotherapy. I think out of the study design, this is probably the section that I have the the biggest criticism of. I don’t think it was really a fair fight for the nerve to be compared to single agent chemotherapy, because in most cases, I think Joanne acknowledges would offer a combination of one of these chemotherapies with bevacizumab in the setting of platinum resistant ovarian cancer.

00:24:32:19 – 00:25:01:15
Unknown
And I would have loved to see Avastin actually included in that other arm. That being said, the primary endpoint was progression free survival and secondary endpoints included overall response rates, overall survival. And then this primary pro analysis is the patient reported outcomes. They also looked at safety and tolerability. This is a new drug, so always looking to see if it’s safe and how patients tolerate the treatment.

00:25:01:17 – 00:25:28:02
Unknown
Duration of response. DLR is another really important outcome, especially in cases of treatment resistant disease, because you don’t only want to see if they respond, you want to see how long patients respond for, if they respond and then again, you see that PFC to add another secondary endpoint. And so these again, these were results that were previously reported.

00:25:28:04 – 00:25:56:05
Unknown
See this kaplan-meier curve, which becomes pretty familiar after you look at enough of these trials. And so this top left graph is looking at progression free survival as a primary end point. And you can see that the hazard ratio is 0.65. So the merged group and it was 35% less likely to progress on treatment than the chemotherapy arm.

00:25:56:07 – 00:26:25:04
Unknown
And interestingly, this bottom left graph looks at overall survival. And I had mentioned during the discussion an earlier trial that overall survival difference is really hard to show in ovarian cancer. But you can see here that there is an overall survival advantage to treating with Merv over chemotherapy with a hazard ratio of 0.67. So both of those are really exciting results.

00:26:25:06 – 00:27:08:21
Unknown
The secondary endpoint, the objective response rate, you can see that the rate is significantly higher in the Merck group with 42.3% of patients responding. And the overall response rates include complete responses, partial responses and stable disease. And so that’s versus basically 60% in the chemotherapy arm. And that represents a difference of 60, I’m sorry, 26.4% safety findings. Fewer patients had a grade three or greater adverse events in the Merck arm and fewer patients had discontinue treatment because of adverse events in the arm.

00:27:08:23 – 00:27:44:04
Unknown
And so showing really positive cancer related outcomes and improved safety and tolerability over chemotherapy. It’s important to remember at the point of platinum resistant, many of these patients have seen several lines of chemotherapy and in cases in those, such cases can be more sensitive to the toxicity is chemotherapy. So having alternate treatment is very beneficial versus the side looking at patient reported outcomes.

00:27:44:07 – 00:28:22:17
Unknown
They used this pro assessment tool, which mainly evaluates abdominal and GI symptoms, looking at things like abdominal pain, bloating and patients reporting that their close feels too tight. So again, abdominal distension, bloating, bowel habits, gas and feeling too quickly after eating early satiety. And so they looked at patient reported outcomes at several different time points. Initially they reported the the patient reported outcomes between week eight and nine.

00:28:22:19 – 00:28:51:17
Unknown
And you can see at this point there really isn’t a meaningful difference between the two treatment arms. But when you look at sustained improvements like how do patients do at subsequent endpoints at 15 weeks or 24 weeks, the symptom improvement was more sustained in the Merve arm than in the chemotherapy arm. So another sort of positive result from this trial.

00:28:51:19 – 00:29:23:24
Unknown
And so the conclusions are that patients treated with Merve are more likely to maintain or improve an over ovarian cancer specific measure of quality of life improvements than the patients given chemotherapy. And Merve demonstrated a statistically and clinically significant improvement in progression free survival overall response rates, Overall survival one compared to investigator choice chemotherapy. So all really exciting results.

00:29:23:24 – 00:29:49:21
Unknown
And of course, the authors of the trial concluded that this should be a new standard of care for patients with folate receptor, alpha positive, platinum resistant ovarian cancer. And I think to some extent that statement is true. And since this has a potential of becoming a new standard of care, I thought it would be helpful to spend some time on the unique side effects associated with Merv.

00:29:49:23 – 00:30:24:09
Unknown
And so I think one of the most unique and interesting of the side effects is eye toxicities and these can actually be quite common with up to 30% of patients reporting some kind of blurred vision or dry eyes, sensitivity to light pain of redness. And because of that very specific outcome, it’s actually standard recommendation for patients to see an ophthalmologist who is trained in recognizing these side effects and see an ophthalmologist before treatment starts.

00:30:24:09 – 00:30:51:22
Unknown
And then every two cycles or like eight weeks or so while on treatment pneumonitis. Lung toxicity is another common side effect. Pneumonitis is an important one because it can be severe or life threatening. And so it’s really important to monitor for signs of trouble breathing, shortness of breath, cough or chest pain. And of course, to share the side effects with your your doctor.

00:30:51:24 – 00:31:34:24
Unknown
If you’re on this medication and you start experiencing those things, peripheral neuropathy, I think, is one of the more difficult side effects of this therapy, because, as you know, a lot of patients who have already received carboplatin and PACLITAXEL will have some residual neuropathy from their treatments. And so being on Merv can add to that. So again, very important to monitor for signs of worsening numbness, tingling, burning and other neuropathy symptoms, the toxicities are so unique and so important that the drug manufacturer actually provides a lot of resources, reminding patients when to take preventative eyedrops.

00:31:35:01 – 00:32:02:00
Unknown
Then there’s actually an app that will text your phone and tell like remind you want to take the eye drops throughout the day. Just that can try to minimize that side effects. And last but certainly not least, is a phase one trial that I wanted to present to everybody looking at RDX monotherapy in patients with previously treated ovarian cancer.

00:32:02:02 – 00:32:45:07
Unknown
And this is a phase one trial. So really the goal of a phase one trial is to look at safety and find appropriate dosing. But at the same time, you can also gather information about treatment, response and efficacy of the drug. RDX. DX is another antibody drug conjugate, and it’s comprised of a humanized antibody against a protein called CD six and the chemotherapy drug that’s attached to it is to isomer ACE inhibitor, which is a commonly used chemotherapy drugs in many different types of cancers.

00:32:45:09 – 00:33:09:20
Unknown
And so the study design for this Phase one trial, Part A is a dose escalation. So they basically started a low dose and increase it until it’s felt that they’ve reached the maximum tolerated dose and then they’ll do a dose expansion where they select the doses that they found from part A and look at additional patients in a part B to really test that.

00:33:09:20 – 00:33:47:14
Unknown
Those are the the safest and the most appropriate doses. And so what safety data were they able to get from the phase one trial? And the conclusion was generally that the drug as well tolerated most of the side effects are in the grade 1 to 2 categories. So mild manageable symptoms. You can see from the list on the right that most of the more significant symptoms are GI related and which of course can be tough, especially in platinum resistant patients.

00:33:47:16 – 00:34:20:10
Unknown
So nausea, vomiting, diarrhea, side of the spectrum, constipation is there decreased appetite and then dehydration. I think that all goes with just a constellation of GI upset, the sort of category of side effects that I think were more likely to be grade three are the bone marrow toxicities. So anemia, neutropenia, the white counts being affected and platelets being decreased.

00:34:20:10 – 00:34:58:23
Unknown
And so I think basically GI bone marrow toxicity seemed to be the most important of the ones that were reported at ASCO this year. The preliminary results also gave us an idea of antitumor activity. And I think that this is a really exciting slide. The overall response rate you can see confirmed overall response rate was 48.6%. And so typically when we’re looking at results from a phase one phase, phase one trial to decide should it be moved on to phase two, we get excited if we see an overall response rate of 20 to 30%.

00:34:58:23 – 00:35:34:08
Unknown
And so a 50% response rate is really exciting. And this overall response rate of almost 50% included one complete response 17 Partial responses, 18 stable disease and no patients that progressed. So that’s really exciting. That translates to a disease control rate of about 90.4%. Another exciting and great with this trial is the median duration of response. So I mentioned earlier, overall response rate is important.

00:35:34:08 – 00:35:56:23
Unknown
We also want to know how long patients respond for. And you can see this duration of responses is close to a year and the median time to treatment, it takes patients a little bit less than six weeks to start responding to this therapy. And the median progression free survival is 8.1 months. So all really exciting data for a phase one trial.

00:35:57:00 – 00:36:24:12
Unknown
And so conclusions are the well statement is that RDX D is the first CD eight six directed ADC to demonstrate promising efficacy and heavily pretreated patients with ovarian cancer. Efficacy does not seem to be dependent on the level of CD six. So you might remember from the Merv Trial, patients were only offered the treatment if they had a high folate receptor levels.

00:36:24:14 – 00:36:59:07
Unknown
But the the number of CD six receptors didn’t seem to matter, which is also exciting because this could represent like a universal, a universally available option for patients. We talked about overall response rate was very promising, immediate median duration of response, median progression free survival. The toxicities appear to be manageable and with a 50% overall response rate. This has been moved to the next phase, a phase two three trial that has been initiated globally.

00:36:59:09 – 00:37:45:05
Unknown
I looked this last evening at the cancer dot gov clinical trials and it looks like right now it’s only open in Japan, but it has been assigned a numeric. Georgi the American coalition. It’s been assigned a number for the Georgi. So I’m hopeful that this will be open in the US as well sometime soon. And so the clinical design for that Phase two three trial that hopefully up and coming patients will be included if they have high grade serious or enemy tried ovarian cancer, 1 to 3 prior lines of treatment which can include bevacizumab platinum resistant disease, these patients are required to have already received.

00:37:45:05 – 00:38:10:09
Unknown
Merv, I think the Merv data was so promising that to get into the ethics of enrolling patients in clinical trials, the authors of this clinical trial likely felt that patients should be offered more before being offered a new therapeutic. And of course they couldn’t have any prior lines of similar agents. And so the Phase two trial will include the different doses.

00:38:10:09 – 00:38:43:14
Unknown
Again. And then from that additional dose, finding phase, then they’ll transition over to the phase three trial, which will compare the dose discovered from phase two. Now compare that to single agent gemcitabine and doxorubicin to take in or paclitaxel basically doctors choice and that’s that. So in summary, PARP inhibitors continue to show the most profound improvement outcomes for patients with ovarian cancer.

00:38:43:14 – 00:39:14:04
Unknown
And this is most significantly in patients of the bracket mutation. Bevacizumab remains an important targeted therapy, especially in the maintenance and and in the platinum resistant setting. Merv improves progression free survival and overall survival. Well compared to single agent chemotherapy in patients with platinum resistant ovarian cancer in RDX, DX demonstrates promising efficacy in heavily pretreated patients and is moving to phase two three trial development.

00:39:14:06 – 00:39:39:12
Unknown
We continue to explore the potential role of immunotherapy in ovarian cancer, but so there really haven’t been many positive trials showing that immunotherapy is effective for ovarian cancer. Because me and my partners at SGA this year, it’s Dr. David West on the left. She practices at Northern Westchester Hospital. And Dr. Janine Villella is my partner here at Lenox Hill.

00:39:39:14 – 00:40:07:03
Unknown
Thank you so much for having me. And I would love to take any questions now. Thank you so much, Dr. Perera, for breaking down all of these findings and such an understandable way. So now let’s start the Q&A. There were a lot of pre submitted questions, but you can also still submit questions in the Q&A section at the bottom of your screen.

00:40:07:05 – 00:40:35:08
Unknown
We will try to get through as many questions as we can in remaining time. All right. Let’s let’s dive in. So not surprisingly, there are a lot of questions about murder, and one of them is how long can patients stay on it More than the trial. Would it? Let me just look back because, again, these are like new treatments.

00:40:35:08 – 00:41:05:07
Unknown
I actually have not had anybody on it for longer than a few months so far, Master these trials in patients who have gotten resistant disease. The recommendation for the treatment is to continue until progression or until toxicities. And so I don’t know if that timeline has been necessarily defined because, of course, it will be different for all different patients.

00:41:05:09 – 00:41:36:21
Unknown
Got it. And then this person specifically asking for the actual increase in overall survival in months for those on Merv in the trial, the actual increase in month, so to say, increase in months, if you define it as like median progression free survival. Let me look back at the have a look graph here. It’s teeny tiny.

00:41:36:23 – 00:42:09:07
Unknown
And so, you know, hard to say it that way. And so when you want to see improvement in months, we can say at median progression free survival, meaning overall survival, we can compare that. And so the median overall survival crosses 50% at around 12 months for the patients who are not on the drug and around 18 months for the patients who are.

00:42:09:09 – 00:42:38:19
Unknown
And so that’s about an eight month overall survival advantage just based on quickly looking at the graph. So very meaningful, very much so. And then we’re also getting a lot of questions about sleeper cell ovarian cancer. And so I’m just wondering if there’s any updates or any research in the pipeline that you could provide related to clear cell ovarian cancer?

00:42:38:21 – 00:43:15:04
Unknown
Yeah. So I didn’t see any positive studies out of issue this year. I know there are many ongoing studies looking at sort of basket trials and things, looking at specific mutations that affect your cell and whether or not we can use targeted therapies. But I’m not aware of anything that’s been reported this year. Thank you. And then we’re we’re getting questions about the length of time that patients can stay on bevacizumab after first line treatment.

00:43:15:06 – 00:43:45:08
Unknown
Yeah, that’s a great question. So after that line treatment, the defined amount of time is just the, you know, what the trial showed. But I think in the recurrent setting is when we start using Avastin with sort of a no end point and side. And I think it goes back to what I said about Merve is that you can really continue it until progression of disease or until toxicities.

00:43:45:10 – 00:44:14:05
Unknown
And I have had patients on bevacizumab three years and they tolerate it really well and it keeps the tumor at bay. And I think that for me that is the most important setting to use bevacizumab and that’s generally well tolerated. Patients don’t feel like they’re on chemotherapy and it ends up providing a very long interval or can provide a long interval between chemotherapy regimens.

00:44:14:07 – 00:44:49:03
Unknown
Thank You and then going back to our study and that trial, this question is about how many prior lines of chemo were allowed and also how do you do you need to test for the CD six or how do you test for it? So so you don’t, you don’t they actually that was one of the really important statements from that initial phase one trial was that they were seeing in a positive effect whether or not patients had an overexpression of the CD six.

00:44:49:05 – 00:45:05:20
Unknown
And I believe based on the study schema, at least for this phase two three trial, that is kind of slowly opening, it was 1 to 3 lines of prior treatment, but I’ll double check. Yeah, one, two, three lines.

00:45:05:22 – 00:45:36:15
Unknown
Great. Thank you. And then I we were getting some questions also about low grade serous ovarian cancer. And someone specifically asked about the results of the ramp 201 trial. And then I also know that there’s the phase three trial, I believe that’s recruiting now. So I was wondering if you could talk a little bit about that. Yeah, I’m not as familiar with those trials, unfortunately, and I’m so sorry if I had known ahead of time that these would have been questions.

00:45:36:15 – 00:46:17:11
Unknown
I would have probably dedicated some of the time from the talk today to discuss those that we have. Yeah, we’re getting a lot of questions about some of the rarer they’re rare it might be worth doing a session on rare cancer types we do we have some coming soon and then we’re getting questions about how about how often or what’s recommended for surveillance while on Merv and type like chemo scans.

00:46:17:13 – 00:46:47:14
Unknown
Scans. Yeah. So how often do you do? Scans is usually controversial and becomes a little bit of like physician choice. And so in some cases I will monitor symptoms and see when 25 and really not over scan patients. As long as all of those metrics are looking good and you get to know your patients a little bit like I have for some patients, I know they’re still on 25 is really a great indicator of what’s going on with their disease.

00:46:47:16 – 00:47:12:24
Unknown
For some patients to see what 25 is not as great and then I’ll usually scan them like every three cycles or so. But there isn’t. If you look at the guidelines, there isn’t a standard for like how you should do that. That’s why there are so many questions. Patients have so many questions about it because it’s it’s not uniform and then some questions about PARP inhibitors as well.

00:47:12:24 – 00:47:39:01
Unknown
And we do get this question a lot, but can olaparib be taken for more than two years? And if so, are there benefits to that? Yeah, so that’s but that question specifically has not been studied. And so the two years is based on how that initial trial was designed in Europe or at the just interestingly, the trial was for three years.

00:47:39:03 – 00:48:04:02
Unknown
But what’s interesting is when you look at the kaplan-meier curves, when you look at those progression free survival curves, the effect of the Lynparza seems to continue even after treatment. And so I think that is a takeaway that most German ecologists have gleaned from that data and long term data that there’s no clear benefit to continue it for longer.

00:48:04:02 – 00:48:32:05
Unknown
And then you worry about the toxicities and kind of the scary toxicities of continuing it longer, like secondary malignancies and things like that, like leukemia. Yeah. So we also got a question about, you know, the risks of M.D.s and AML. So maybe you could talk a little bit about that. Yeah. So overall, the risk is still low and most of the PARP inhibitors trials report a risk of like 1 to 3%.

00:48:32:07 – 00:49:07:18
Unknown
And so the risk is really low, but it’s hard to say if that risk would increase incrementally if you continued beyond that the time frame that was described in the studies. Okay, great. Thank you. And then we’re getting questions about just looking whether another question about PARP inhibitors overall, but whether the side effects improve over time. Yeah, that’s a very interesting question.

00:49:07:18 – 00:49:38:09
Unknown
So they actually it has been shown that the side effects in the PARP inhibitor are typically the most significant in the first month on treatment, which is kind of counterintuitive when you think about how patients respond to chemotherapy. Usually chemotherapy, it’s like the the toxicities build on themselves and they feel worse over time. But with PARP inhibitors, the fatigue and some of the quality of life affecting side effects tend to be worst at the beginning of the first month.

00:49:38:11 – 00:50:07:24
Unknown
But I usually try to convince patients to stick it out for the first 1 to 3 months to see if after some time their symptoms will improve. Right. And then we also we have a question about the use of estrogen blockers for ovarian cancer. Yeah. And so there aren’t, there aren’t great trials to support using estrogen blockers.

00:50:07:24 – 00:50:46:05
Unknown
I think by themselves they are not very effective. I have definitely used estrogen blockade in some of the low grade tumors, but I grade serous tumors. There isn’t a lot of evidence to support using like aromatase inhibitors and the estrogen blocking tumors. So could you talk a little bit more about it in terms of low grade? And so in low grade, we have actually found that patients can benefit from maintenance and aromatase inhibitors.

00:50:46:07 – 00:51:12:22
Unknown
And so the standard of care is still to give chemotherapy, but now with maintenance, estrogen receptor blockers and that the outcomes are improved that way, most of us still don’t feel comfortable giving up on chemotherapy altogether, and we don’t have data to support doing that. And so is more like addition rather than subtraction at this point.

00:51:12:24 – 00:51:42:06
Unknown
Thank you. And then we got this question wondering if you know of any of these blood tests and whether they’re widely used or effective in diagnosing ovarian cancer like over a watch or over one plus. Yeah. And so what’s interesting about those is that they all could see 125 And so it’s a little bit hard to flush out.

00:51:42:08 – 00:52:08:07
Unknown
I think in the general gynecology world, those have started to be used a lot more. But, you know, colleges still very much rely on see 125 and then, you know, that’s those are really used more in the pre like the you know, there’s no cancer there yet and you’re trying to decide if an ovarian cyst is something concerning or something benign.

00:52:08:09 – 00:52:31:00
Unknown
And I think that the same 25 and imaging studies are the most informative. And so none of my colleagues are really using those other studies currently. Sometimes they get those results and then I look at the breakdown. I’m like the saw from the C 125. Like I think those other things are very helpful. All right. Interesting. Thank you.

00:52:31:02 – 00:53:06:17
Unknown
And then we’re getting a a sort of a follow up about whether you could explain, again, the progression free survival figures and or what progression free survival means. But I think is really important for you to understand that it’s the most important time point where we’re looking at these trials. So progression free survival is how you define the time from the complete action of treatment to cancer, recurring and progression free survival can be described as a median progression free survival.

00:53:06:19 – 00:53:31:04
Unknown
And that’s really when we’re trying to say how many months are gained by this treatment. The question that was asked earlier, most of the time you’re talking about median progression free survival because you want to see how long did it take 50% of patients to recur in one arm versus 50% of patients in the other arm. And the median progression free survival can also be described as a percentage.

00:53:31:06 – 00:53:57:10
Unknown
And so there are some trials where they’re really excited about the outcomes. They want to get the results out quickly. So they’ll say, okay, let’s just describe the progression. Free survival was at three years. They don’t wait for the median progression free survival to happen. They don’t wait for 50% of patients to recur. And so then they’ll say at three years, 20% of patients in the experimental arm versus 50% of patients in the placebo arm had recurred.

00:53:57:12 – 00:54:26:13
Unknown
And so when you look at the difference and that difference is usually reported as a hazard ratio. Great. Thank you for explaining that again. And then we have a question of asking your thoughts on Signatera testing. So I love this question because actually all of my fellowship research was in circulating tumor DNA, and so I would maybe explain what that is and the results of that.

00:54:26:16 – 00:54:57:11
Unknown
Yeah. So I think this is where I get really excited and probably more excited about potential here. And so we know that cancer is driven by gene mutations and so the cancer cells will have a DNA profile that’s different than normal cells. And when cells die, they kind of like burst and release that DNA into the circulation. And so there’s an opportunity to detect these fragments of DNA in the circulation.

00:54:57:11 – 00:55:17:06
Unknown
And this can serve as a tumor marker. What makes this a really interesting tour marker is that it’s very specific. If that mutation is there, that means the cancer has to be there, whereas C 125 can be elevated, I’d say about 25 elevated because a patient had pneumonia and had nothing to do with their cancer. 6125 is not specific.

00:55:17:06 – 00:55:55:03
Unknown
It can be elevated for other reasons, but if you see cancer specific DNA fragments in the blood, you know, the cancer has to be there. So it’s specific. It also gets degraded very quickly, circulating DNA can only survive in the blood for like 2 to 4 hours. And so, you know, in real time exactly whether or not the levels are detectable, we’re assuming 25 is a protein takes longer to degrade and can actually linger elevated for up to a month after it’s not meaningful anymore.

00:55:55:05 – 00:56:34:15
Unknown
And so I think Signatera is really interesting. Signatera is basically a test where they they take a sample of the tumor, they figure out which mutations are present in that tumor, and then they create a patient specific blood test to try to sort of discover a patient specific tumor marker, which can be very specific and sensitive and the turnaround time from when the tumor is tested to when you can have a usable tumor marker, I think is like 4 to 6 weeks and it hasn’t been.

00:56:34:17 – 00:57:06:22
Unknown
So it’s been shown that you can detect the tumor DNA in the circulation. What hasn’t been really looked at and I think they’re collecting data now, is how to use that information. Is it prognostic? Is it being there on treatment? Does it matter? Like how do we use this? And and there will, of course, be patients where the circulating DNA is never detectable and it’s just not a good two marker for them to say my C 25 is not a good two marker for some patients.

00:57:06:24 – 00:57:36:06
Unknown
But I think it could potentially serve as a very sensitive and specific tumor marker for patients better than C 125 that is, that is exciting. And then we have a question about High Park and you know if there’s any updates on on that. Yeah. So there are no high spec updates at ASCO this year but I think that high peak is another really interesting opportunity in our institution.

00:57:36:06 – 00:58:17:18
Unknown
We offer high peak in the interval debulking setting and that’s actually the only setting that the data supports using it in by interval debulking. I mean those patients whose cancer is not respectable at the beginning, those are the patients that will get chemotherapy upfront, typically about three cycles, and then they go for their debulking surgery at time of that debulking surgery, there is a significant benefit to giving Hyde Park, at least based on two clinical trials, giving it in other settings like recurrent disease or in the upfront upfront setting.

00:58:17:18 – 00:58:47:01
Unknown
Those are all negative trials. But I think that in my experience I package generally well-tolerated. It adds about 3 hours of surgical time and I think the benefit is profound enough to make it worth it. I think that’s really where the role of IPI intraperitoneal chemotherapy has ended up going. I’m not familiar with many junior colleges, at least New York City.

00:58:47:01 – 00:59:15:03
Unknown
They’re still giving traditional IPI chemotherapy. In a lot of ways we’ve shifted to giving high peak. Thank you. And so we only have time. Looks like for one more question. So I just want to conclude with, you know, what is your biggest takeaway for patients out of all of this information that you presented today and these latest updates?

00:59:15:05 – 00:59:49:03
Unknown
I think that these are all really exciting results. I think that the two trials that I presented with the ADCs are exceptionally important. It’s the platinum resistant disease that we’re constantly hoping for more options. And I think that is fairly well tolerated and new therapies with really great improvements in progression free survival and overall survival, I think those are the most exciting of the updates that we got out of Astro this year.

00:59:49:05 – 01:00:19:08
Unknown
Great. Thank you so much, Dr. Perera, for this informative program and answering all of these questions and thank you to all of you who participated today and submitted your questions. We please make sure to check out Cher’s upcoming educational programs and support groups and follow us on social media. We also ask that you please take a moment to complete the survey.

01:00:19:08 – 01:00:42:17
Unknown
At the end of the webinar, the survey will show up in your browser when the webinar ends and the link will be also be sent in a follow up email. All surveys are anonymous and we really use that feedback to inform our programing and make any improvements that we can. So thank you for taking that and that concludes today’s webinar.

01:00:42:17 – 01:00:51:13
Unknown
Thank you again, everyone. And thank you again, Doctor. PEREIRA My pleasure. Thanks so much for having me. Have a great day, everybody. You too.