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

May 22, 2024

Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.

00:00:00:00 - 00:00:53:05
Unknown
Hello and welcome to today's webinar report back from SGO: What's the latest in cervical cancer? I’m Aisha McClellan, the cervical cancer program coordinator at SHARE. Today's webinar will focus on any new information and research advances from the society of Gynecologic Oncology annual meeting in March before the presentation begins. I'd like to tell you a little bit about Share Shares, a national nonprofit that supports, educates and empowers anyone diagnosed with breast or gynecologic cancer and provides outreach in general public about signs and symptoms because no one should have to face breast, ovarian, uterine, cervical or metastatic breast cancer alone. s

00:00:53:07 - 00:01:18:19
Unknown
For more information about upcoming webinars, support groups and helplines, please visit our website at Share Cancer Support dot org. All participants will be muted during the presentation. Once Dr. Co finishes, presenting will be in the Q&A session. Feel free to ask any questions during the Q&A section at the bottom of your screen. Remember that Dr. Ko is unable to give specific medical advice, so please keep your questions general in nature.

00:01:18:21 - 00:01:40:18
Unknown
We also have closed captioning available. 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 are very excited to have Dr. Co joining us today as our speaker and now I'd like to hand it over to Dr. Ko to introduce herself.

00:01:40:20 - 00:02:16:03
Unknown
Wonderful. Thank you so much for that wonderful introduction and I will just give a very brief intro about myself. So I am a gynecologic oncologist, associate professor at the University of Pennsylvania here in Philadelphia. I have the privilege to take care of patients with gynecologic cancer, as well as patients with complex gynecologic conditions. And additionally, I am a physician researcher with an emphasis on health services research, and primarily that means thinking about how we are able to provide care to our gynecologic cancer patients.

00:02:16:04 - 00:02:35:02
Unknown
How do we ensure that we have policies that that really fulfill the best delivery of care and access to care to everyone that has driven cancer? And by bridging my daily work with, you know, a lot of data science as well as research and thinking about how we can actually enact policies to ensure that everyone gets the care they need.

00:02:35:04 - 00:03:07:21
Unknown
So thank you so much for the opportunity to speak today. And without further ado, I will bring up my slides and let me just make sure we have the set of slides here and I'm going to make it full screen. Wonderful. So thank you again for the opportunity to report back from SGA 2020 for our annual meeting in March.

00:03:07:23 - 00:03:32:20
Unknown
What's the latest in Cervical cancer? And here my disclosures. So for today's talk, I'd like to present an overview of cervical cancer update. First, talk briefly about cervical cancer. What is it? And also the epidemiology. You know, how common is it? And then what are efforts for eradication of cervical cancer? Talk some about updated staging and most importantly, talk about treatment for cervical cancer.

00:03:32:20 - 00:03:57:01
Unknown
Where are we at? So cervical cancer, let's define the disease. Cervical cancer develops from the cervix, which is basically the bottom portion of the uterus, as you can see here on the diagram. And the most common type of cervical cancer is squamous cell carcinoma followed by adenocarcinoma. There are other types as well, such as neuroendocrine clears cell and others that are certainly most common.

00:03:57:03 - 00:04:25:06
Unknown
Now, cervical cancer is the fourth most common cancer in women in the world. It is generally caused by persistent infection with the human papilloma virus called HPV. And we do know that prophylactic vaccination, meaning preventive vaccination and screening tests, are effective to prevent pre-cancer conditions, as well as cervical cancer itself. And when we talk about pre-cancer conditions, that's frequently referred to as dysplasia or pre malignant.

00:04:25:08 - 00:04:49:15
Unknown
So, as stated, cervical cancer is largely driven by the human papillomavirus called HPV. And in fact, HPV cause about 95% of all cervical cancers. As you can see in this table on the left, HPV virus is also associated with other cancers of the body in women, including anal cancer, vulvar cancer and additional cancer. But these are far fewer compared to cervical cancer.

00:04:49:17 - 00:05:13:06
Unknown
And, of course, HPV is associated with cancers in men as well as listed. And it does usually take some years of HPV effect on the cervical area before it becomes truly cancer. So that's why there are screening tests to be able to catch these catch these changes before it develops into cervical cancer, as you can see in the bottom diagram.

00:05:13:08 - 00:05:45:14
Unknown
So how do we actually do these screening tests? Traditionally, we have things called the pap smear, as people refer to it, as well as HPV testing. So what this involves is a pelvic exam done by a physician or a health care provider to actually look at the area, the vagina, the cervix. Usually in an office setting. And also there's a component of a manual exam where you actually palpating with your hand to see what those cervix vagina pelvic organs feel like.

00:05:45:16 - 00:06:09:04
Unknown
So people will usually refer to the pap test as a pap test, otherwise known as a Papanikolaou test or now cervical cytology test. These words are all used interchangeably. Basically, it refers to obtaining a sample, the free cells of the surface of the cervix using a broom or a spatula with a side of brush. You can see in the diagram here how that's done.

00:06:09:06 - 00:06:37:07
Unknown
Additionally, there's the HPV test, which is collected at the same time frequently as the PAP test itself. And again, you're using the same broom or brush or spatula to do this. And it's basically run off the same sample that's being collected by your health care provider. Now, if the PAP test and HPV test comes back positive or concerning for abnormal condition, usually it leads to doing colposcopy and biopsies in the office as a next step.

00:06:37:09 - 00:07:04:24
Unknown
So as you can see here, this is again performed in the clinic setting. It does not require any special anesthesia. It generally is quite tolerable, could have a little bit of discomfort, but is very tolerable and involves looking at the cervix directly with a magnifier like you can see here, and then doing directed or random sampling biopsies where you're taking a tiny piece of tissue and examining under the microscope to see what is really going on there.

00:07:04:24 - 00:07:48:10
Unknown
If it is pre-cancer or possibly cancer. Additionally, if there is a diagnosis of cancer based on that colposcopy biopsy, additional tests are usually done in order to identify whether the area involved is limited to the cervix or possibly beyond the cervix. And so there are different types of imaging studies that we use, such as comic ultrasounds that give a general idea of if there's something abnormal in the in the uterus, cervix, ovarian areas, but more specifically, we have, for example, MRI, pelvis, which can provide details of the cervical architecture, especially if there's a tumor present in that area, as well as if there's any metastatic lesions, meaning tumor elsewhere.

00:07:48:12 - 00:08:13:18
Unknown
There are also things such as CT scans that again, can provide details regarding metastatic lesions, especially in the chest, abdomen, pelvis, and it's very fine tuned for that. And lastly, PET scans also can provide details regarding areas of disease in the cervix as well as beyond the cervix throughout the body, and can actually provide details regarding activity of these lesions.

00:08:13:20 - 00:08:41:14
Unknown
In general, your health care provider can help decide which tests might be best given your specific condition. So again, how common is it? How common cervical cancer in the U.S., approximately 13,800 new cases of invasive cervical cancer will be diagnosed in 2024 and about 4300 women will die from the disease in the year. And overall, the lifetime risk of cervical cancer is about 0.7%.

00:08:41:16 - 00:09:03:02
Unknown
And you'll see in the graph here on the right that most women are diagnosed with localized disease, meaning the cancer is just pretty much in the in the cervix itself. And that's actually a good thing that these cases are caught before it's widely spread. Now, we do know cervical cancer incidence and mortality in the U.S. has improved over time.

00:09:03:04 - 00:09:33:13
Unknown
You can basically see on the top line that the number of cases of cervical cancer each year are actually dropping and the number of deaths are actually dropping as well based on the on the bottom green line. And you can see that over the time that HPV vaccine in situ in 2006, followed by COTESTING or TAPS, plus HPV testing in 2012, as well as HPV alone, testing in 2018, I think have certainly played a large role in seeing the decrease in cervical cancer.

00:09:33:15 - 00:10:00:21
Unknown
However, cervical cancer is still present. It's certainly not eradicated and in fact, it's actually affecting some populations more than others, even in the U.S. And what we've seen is that certain populations by race, for example, the Hispanic population, the black population, and also the Native American population, are certainly affected more by cervical cancer than, for example, the white population.

00:10:00:23 - 00:10:24:14
Unknown
And you can see the brown squares reflect the black. The blue triangles reflect the Hispanic population. The green triangles reflect the Native American. And they're just those lines are higher up, meaning they're more cases each year diagnosed with cervical cancer in those populations in the white. Ultimately, I think we're all trying to eradicate cervical cancer as a ultimate goal.

00:10:24:16 - 00:10:47:11
Unknown
And here, just again, reflecting the difference in populations, we can see here that black population have a higher incidence, meaning they're more cases of cervical cancer. The fact that group. And then there's also actually the highest death rate in that group as well. But certainly it is affecting the Native American, the Hispanic, as you can see, in the bottom bars as well.

00:10:47:13 - 00:11:15:07
Unknown
So where are we now and how is this being seen across the country? This was a study presented by Dr. Castellano at all at our annual meeting. And what they did is they looked at several data sources, including insurance data sources, as well as the U.S. Census, as well as treatment data sources with the American Brachytherapy Society to see where the cancer cases happening and what are the social factors behind it.

00:11:15:09 - 00:11:37:21
Unknown
And so you can see here from the map that they presented that this is a map of the U.S. and that there are cervical cancer cases across the U.S. that are occurring. Those that go to the purple and almost dark purple areas are where the burden is. The highest. So CC reflects cervical cancer burden. You can see what states are affected the most.

00:11:37:23 - 00:11:59:05
Unknown
Some in the more Southern states cross across from the west to the east. And then you can also see where there are treatment centers, for example, brachytherapy and radiation treatment centers that are available. And of course, there are some disparities where there are lots of, you know, dark purple areas that don't necessarily have treatment centers really nearby them.

00:11:59:07 - 00:12:25:15
Unknown
But what we can see is that the social ramifications, you know, that poverty level on screening and disease is associated. So, again, Dr. Castellano demonstrated that a higher percentage, low income households in region are correlated with less screening for cervical cancer and actually a higher burden of cervical cancer as well. So we realize that, yes, more screening is needed.

00:12:25:17 - 00:12:52:19
Unknown
There areas in the country especially and socially economic maybe lower resourced areas that really could benefit from more resources, more testing, more treatment options for these patients. And what we can see is that when you do have treatment services available, meaning radiation, brachytherapy centers available, that in fact there appears to be less burden of cervical cancer cases that are metastatic.

00:12:52:21 - 00:13:18:02
Unknown
So, again, having the resources in the places where we have the most cancer cases actually has a better outcome. So what are all the efforts to eradicate cervical cancer? We've now talked about the burden of disease and how it impacts populations across the U.S.. What are our efforts to eradicate it? So there is a international effort really based emphasizing this.

00:13:18:04 - 00:13:49:10
Unknown
The World Health Organization has initiated a cervical cancer elimination campaign back in August 2020, and they're hoping by 2030 that we can achieve these goals. Number one, vaccination, 90% of girls are fully vaccinated with the HPV vaccine by the age of 15, screening that 70% of women screened using a high performance test by the age of 35 and again by the age of 45, and treatment that 90% of women with pre-cancer are treated and that 90% of women with invasive cancer are managed.

00:13:49:10 - 00:14:16:18
Unknown
And this is a worldwide goal. So what are we doing in the U.S.? The Society of Gynecologic Oncology has a cervical cancer taskforce that is led by Dr. Mark Einstein, Dr. Damnatio and this group is dedicated to reviewing, providing guidance regarding vaccination screening, management of cervical cancer. And partnering with the goals of the W.H.O., which we just mentioned to achieve these goals to eradicate cervical cancer.

00:14:16:20 - 00:14:44:04
Unknown
We want to collaborate and advocate with other medical organizations and really expand the global training program with a focus on surgical management to be able to provide treatment to women with cervical cancer throughout the world. And so here there's an opportunity to participate, including patients and patient advocates. You know, we are hoping to amplify the the voice about cervical cancer knowledge, information and treatment opportunities.

00:14:44:06 - 00:15:14:15
Unknown
And here's a contact. If you're so interested in joining the effort, just go to old on the issue dot org. Also, Foundation for Women's Cancer again is dedicated to providing cancer awareness and treatment to gynecologic patients throughout the whole country. In the U.S., September is actually Gynecologic Cancer Awareness Month and is a great opportunity to really amplify the the information about cervical cancer as well as biology and cancers.

00:15:14:16 - 00:15:53:20
Unknown
Again, if you're interested, feel free to check out this web page Foundation for Woman's Cancer. And research. And funding is critically important because that is how we actually identify new drugs and bring new treatments and better treatments to cervical cancer patients. And here I wanted to just share with you all what is our sort of funding environment dedicated to different cancers in the country through the NIH, National Institutes of Health, here at the U.S. And you can see that cervical cancer has had some funding available, 57 million back in 2015, up to 73 million in 2021.

00:15:53:22 - 00:16:16:10
Unknown
And that is good. But we are always looking for more support to be able to make more discoveries and have more treatments for our patients. And cervical cancer. You can see relative to other cancers where cervical cancer stands, endometrial uterine cancer is is actually the most common joint cancer, but only funded 14 million ovary cancer is, of course, a concern as well.

00:16:16:10 - 00:16:50:08
Unknown
134 And but compared to breast and prostate cancer, breast cancer gets substantially more funding, as we can see here of 558 million. So, you know, we're always thinking about how we can think about resources to actually investigate cervical cancer research. And here we're going to dive deep into cervical cancer screening, prevention and then treatment. So we realize that there are gaps, challenges, opportunities in cervical cancer prevention, screening and treatment.

00:16:50:10 - 00:17:16:20
Unknown
This was presented by Dr. Cassell at our annual meeting, and we realize that there are barriers, trade barriers include in clinical centers, testing costs and available follow up. There's certainly social barriers to accessing health care like transportation time. There's barriers to having available pathology services and lack of equipment and even barriers to vaccination knowledge, trust society barriers as and others.

00:17:16:22 - 00:18:00:24
Unknown
So what are some of the initiatives to try to overcome some of these barriers? One of the highlights here by Dr. Cassell is bringing about HPV testing of Self-collected specimens. So not requiring a health care provider physician to actually do the collection, but doing it yourself. And what we realize is there are a lot of studies out there and more and more data that suggests that self-collected specimens may be as good at picking up HPV positive cases and being able to then, you know, triage patients to appropriate health care provider to get the next step, sort of that colposcopy biopsy and physical exam evaluation that we've been talking about.

00:18:01:01 - 00:18:23:02
Unknown
And by using this approach that it actually is pretty good, that it could decrease the burden, it can get out into the community more, and that it's actually pretty good at identifying these pre-cancer changes of the cervix and therefore being able to prevent, you know, it becoming cancer, actually being able to pick up these cases before it gets to that point.

00:18:23:04 - 00:18:46:10
Unknown
And with the South collection technique, they found that based on the studies available, it's highly acceptable to the patients. It doesn't require a traditional pelvic exam, which can be more uncomfortable. And one of the concerns that women might have is that they feel like they might not be able to do as good a self-collection as a provider. But in fact, there's more and more data that says maybe it is okay and as good.

00:18:46:12 - 00:19:25:18
Unknown
So in the U.S., there is a big initiative by the NCI National Cancer Institute called the Last Mile Initiative, and they've nicknamed it the Ship Trial Network, or SELF-COLLECTION for HPV to improve cervical cancer prevention. So this ship trial, it is conducted at multiple medical cancer centers across the U.S. But the point is that it's actually testing this self-collection process and ultimately trying to demonstrate that is acceptable, feasible, accurate and able to pick up cervical cancer and cervical pre-cancer conditions for patients across the country.

00:19:25:20 - 00:19:51:16
Unknown
So that's very exciting. And when we think about the W.H.O., again, they also have guidelines that they've put out being the following They recommend using HPV, DNA detection as a primary screening test rather than visual examination or psychology. The traditional Pap smear as we know it in screening and treatment approaches among general population, women just in general, as well as those living with HIV.

00:19:51:18 - 00:20:16:12
Unknown
And the W.H.O. suggests that using this HPV DNA primary screening test with triage or without triage is to prevent cervical cancer. Among the general population, women is the way to go. They do say that when providing HPV DNA testing, they suggest either using samples taken by a health care provider or self-collected among the general population, women and women with living with HIV is appropriate.

00:20:16:14 - 00:20:59:10
Unknown
And they suggest that regular screening interval every 5 to 10 years when using HPV DNA detection as the primary screening test among the general population, women is is appropriate. They also say that screen and treat approach using DNA detection as a primary screening test and suggesting treating women who test positive for HPV DNA is appropriate. The in their screen triage and treat approach using HPV DNA detection as a primary screening test among the general population that additionally using partial genotyping colposcopy visually examining or cytology to treat women after a positive HPV DNA test is appropriate and should be done.

00:20:59:12 - 00:21:33:04
Unknown
And where HPV DNA testing is not yet available operational, then the traditional screening interval of cytology or visual examination every three years is also appropriate. Now, in addition to all the screening tests we talked about, HPV vaccination is also important. And we do know that the HPV vaccine protects against infection from nine HPV subtypes, including the seven types that Cosmo's HPV related cancers as listed as well as the two lowest types that cause most genital warts.

00:21:33:06 - 00:21:59:11
Unknown
And in fact, the vaccine is estimated prevent up to 90% of cancers caused by HPV infection and genital warts. It offers the most protection when given to boys and girls, age 9 to 12, and it is approved for use for adults in the U.S., age up to 45 years, including both men and women. And so the HPV vaccine in general is a total of three injections, the first one, two months, six months later.

00:21:59:13 - 00:22:32:00
Unknown
However, actually, in kids, they state that just two injections are sufficient, given about six months apart are sufficient to give the same protection against HPV virus. And what we realize, though, even though the vaccine is is it's still not widely used and this is in the U.S. as well as worldwide. And this was presented by Dr. Cassell as well in the annual meeting that you can see here, the green reflects the worldwide population, female population.

00:22:32:02 - 00:22:55:10
Unknown
And then there's demonstrating here. The blue is what of those are targeted by actual HPV vaccine programs. And then in the pink are the population that actually got an estimated population actually got the vaccine. So you can see worldwide that there's a lot more opportunity to try to get the vaccine out to the population that really could benefit from it.

00:22:55:12 - 00:23:23:21
Unknown
And you can see that a high income population tend to get more vaccinated. And as we go towards a lower middle incomes, there's certainly less folks that are actually getting it. And this is another study presented by Dr. Wang at the our annual meeting. And this is looking just at the U.S. data. And so what they did is they took in the US this all of US database and rates of vaccination uptake by adults aged 18 to 27.

00:23:23:23 - 00:23:52:18
Unknown
And what they found, there's lower HPV vaccination rates in older middle adults who were unemployed, uninsured and obese, that the burden of health care costs had a negative impact on HPV vaccination rates and that they're with the American Cancer Society. U.S. report was a 65% decline in disease incidents in women aged 2024, while there's a 2% increase in incidence found in women age 30 to 44.

00:23:52:20 - 00:24:21:23
Unknown
So that's just telling us that there is opportunity to get more vaccination out there, that we are not covering all the populations that would benefit from it, and that if we were able to do this, that we can decrease the burden of cervical cancer. So let's talk more now. Diving into cervical cancer, staging as well as treatment. So cervical cancer is generally when you're diagnosed falling that there's a sign stage.

00:24:22:00 - 00:24:44:12
Unknown
And what that refers to as a sort of prognosis, what stage that you're given. If it's localized stage one. Generally has a best outcome, meaning the cervical cancer is only in the cervix area. If it's spread beyond the cervix to the vagina becomes stage two because it spreads beyond that into the other pelvic areas. Stage three if it spreads beyond that, become stage four.

00:24:44:14 - 00:25:15:08
Unknown
And we can use both physical exam as well as imaging studies, as well as pathology information to define the stage. And so here in 2018, we have updated staging guidelines, as you can see here. It is very detailed and it basically tells you by what the size of the tumor is and where it's located, along with adding in radiology information and biopsy information, what ultimately your stage may be.

00:25:15:10 - 00:25:41:09
Unknown
And that is important for several reasons, not only to tell what the prognosis might be for a particular patient, but also when we're thinking about research studies and who gets enrolled into different clinical trials. The stage is actually part of the eligibility criteria for studying different populations of patients with cervical cancer. So diving into treatment of cervical cancer here.

00:25:41:11 - 00:26:17:14
Unknown
Broadly speaking, you know, cervical cancer is are traditionally has been treated with surgery, followed by sometimes chemotherapy and radiation therapy after that. Now, that usually is limited to cervical cancer, where the size of the tumor is less than four centimeters. Now, if the tumor is bigger than four centimeters or the health care provider feels like it is not really a case that surgery is going to be the best option, then the alternative is actually to start with chemotherapy combined with radiation therapy.

00:26:17:19 - 00:26:53:22
Unknown
And that's what you're seeing in this second blue arrow line. So it'd be just going with chemo and radiation followed by surveillance, which is basically monitoring the disease. After that treatment. Now, there are some more novel approaches that are being studied and have been study and that what you're seeing with the bottom line here, if the cancer is spread beyond the cervix, there's the thought to use neoadjuvant chemotherapy, for example, that refers to getting some chemotherapy before actually getting any surgery like a hysterectomy and then possibly falling by adjuvant.

00:26:53:24 - 00:27:18:01
Unknown
So I'll walk you through some of the different clinical trials that are now looking at some of these more novel approaches. As you can see, either doing chemo, radiation with additional medications at the same time, or using this neoadjuvant chemotherapy approach and then into surgery. So here we're going to dive into the granular details of some of the presentations at SGA.

00:27:18:03 - 00:27:41:16
Unknown
This study was evaluation of efficacy in fertility after non radical surgical therapy, extra facial hysterectomy or cone biopsy with pelvic lymph anatomy for stage one one and 1a2 to 1b1 cases. It was presented by Dr. Cummins and his group. This is also called G 278. So it's a prospective study where they were enrolling patients with overall small tumors.

00:27:41:18 - 00:28:03:15
Unknown
So stage one, a one in one, A 2 to 1, B one, so less than two centimeters. And basically the idea is that if we do less aggressive surgery, less radical surgery, it may be just as sufficient with better outcomes for patients. And so the patients had either simple hysterectomy or just a cone biopsy with a lymph node dissection taking out lymph nodes.

00:28:03:17 - 00:28:28:10
Unknown
And what they found ultimately, after enrolling over 200 patients, that the patients actually did pretty well, they had minimal toxicities and that this approach doing less radical surgery for early stage cervical cancer appears to be safe with low complication rate. And so this is just, you know, where are we going? Where is trying to do less aggressive surgeries.

00:28:28:12 - 00:28:54:19
Unknown
Hopefully demonstrating that the patients have better outcomes, less complications, and would do well in the long term. Another study in the surgical space presented at the annual meeting was this one Survival patients early stage cervical cancer after sentinel lymph node biopsy without systematic pelvic event neck. Jimmy This is also nicknamed the Centex trial and was presented by Dr. Sabella at all.

00:28:54:21 - 00:29:36:17
Unknown
And what this was was an international study enrolling patients over 47 sites in 18 countries. And what they're doing here is for women who are undergoing hysterectomy for their cervix cancer. At the same time, they're getting some lymph nodes removed. And historically, a lot more lymph nodes would be taken out called a pelvic lymph node dissection. But now we're trying to do less aggressive surgery, again, by just selectively taking out lymph nodes, by injecting a dye into the cervix at the beginning of the procedure, seeing where the dye travels in the lymph nodes that light up either green or blue, depending what dye you're using.

00:29:36:23 - 00:30:03:04
Unknown
Those are lymph nodes you want to take out. And those are actually the, you know, very high yield for determining if there's any spread of disease. And ultimately, you may only take out 2 to 3, four or five lymph nodes rather than ten or 20. And finding that they're actually pretty good outcomes. So what they found was that when they looked at women in going undergoing this type of procedure, recurrence rate was actually only 6%.

00:30:03:06 - 00:30:34:02
Unknown
And this was comparable to older historic data when they took out a lot of lymph nodes that the recurrence rate was about the same and that the survival patients doing this approach was excellent and comparable to those who had undergo the full lymph node dissection. So again, novel kind of surgical therapies for women with cervical cancer. Now, turning gears a little bit to talk about medications, when we think about immunotherapy, chemotherapy, systemic therapy.

00:30:34:06 - 00:31:04:24
Unknown
What are the advances in this space? So this is where we talk about precision medicine and what is precision medicine. So the NIH has some information about precision medicine. Ultimately, it's where we're not just doing a one size fits all approach. We're actually looking at the different type of, you know, cervical cancers, tumors, etc.. And getting down to the genes, the molecular biology, and being able to then target these cancers in a very much more specified manner.

00:31:05:01 - 00:31:38:20
Unknown
So what we know this is a little background is that cervical cancer cases had been profiled through the Cancer Genome Atlas Research Network, and this was taking a large number of cases, several hundred cases of cervical cancer and looking at literally that gene profile, all these cases. And this was published in 2017. And with that information, it allowed us to identify that cervical cancer may be particularly sensitive to various type of medications, specifically, for example, immunotherapy.

00:31:38:22 - 00:32:09:07
Unknown
And we're going to dive into that in the next few slides. So, for example, presented at the SGA annual meeting neoadjuvant antes Lilly's MAB plus chemotherapy in patients with locally advanced cervical cancer prospective Single arm Phase two Trial. This was presented by Dr. Wenjian Liu and her group, and here their approach was doing neoadjuvant chemotherapy before surgery. So as we mentioned earlier, one idea is actually do some chemo before a hysterectomy.

00:32:09:09 - 00:32:36:09
Unknown
And this was a study done in China, a phase two single arm study enrolled 26 patients with stage one, B three to a two. They were given the Tesla mohammad along with paclitaxel, which is a traditional agent. We use for many decades, plus cisplatin. Again, another traditional agent used for many decades or carboplatin. They take it every three weeks for three treatments and then they go for surgery.

00:32:36:11 - 00:33:10:06
Unknown
And what they found is that these patients overall did quite well. Overall, 87% responded. 65% had a complete response, meaning that basically the cancer was which was fully treated. And looking at under the microscope without pathology, complete response, 60% means that the tumor cells went away. That's actually quite impressive to see. We always think about side effects. 30% of patients had some type of side effects, and of course, those would need to be managed.

00:33:10:08 - 00:33:39:05
Unknown
So that's some novel data and there's going to be more in that space. Another trial that was presented is a randomized Phase three trial of induction chemotherapy, followed by chemo radiation compared with chemo radiation alone and locally advanced cervical cancer. And this was presented at the annual meeting by Dr. Letterman in his group. So the idea here is that we are giving some chemotherapy before getting primary radiation.

00:33:39:10 - 00:34:09:04
Unknown
Chemotherapy. So this is called induction chemotherapy and with paclitaxel carboplatin and then followed by chemo radiation for locally advanced patients with stage one, B, 11b22, two, three, B, and for a cervical cancer. You'll see the criteria here for eligibility. The timing is strict, meaning when you get this induction chemotherapy, B, you have to finish that all in six weeks and then you have to start that primary radiation chemotherapy one week later.

00:34:09:05 - 00:34:38:23
Unknown
So it's right away. And then you have to complete the entire radiation course within 50 days. So this is a protocol that was applied. They enrolled over 500 patients worldwide. Most 70% of those patients were stage two. BE And what they found was in the arm that got this induction chemotherapy, there is a little bit more side effects with low white blood cell count called neutropenia and fatigue.

00:34:39:00 - 00:35:06:20
Unknown
But overall, the outcomes were pretty good. And what they found that ultimately highlighted yellow for induction chemotherapy should be considered standard of care in these cases, and that is feasible across the world. What there's demonstrating, there's improvement in progression free survival as well as overall survival that was statistically meaningfully significant. This here is the algorithm with how they enrolled the patients.

00:35:06:22 - 00:35:44:21
Unknown
So you see you there go in the red group, which is getting the chemo before the primary radiation. Chemo or you go in the blue group, which is the standard chemo radiation. And then they followed everyone up and you'll see their survival curves here, which showed a statistical improvement in progression free survival. The red line with the induction chemo did better than the traditional, and that's shown with the progression free survival graph on the upper left, as well as the overall survival, with a median follow up of over 64 months, which is quite a long time and for that reason it is recommended to consider this approach.

00:35:44:21 - 00:36:19:16
Unknown
Now in subgroup analyzes as well. You can see here that many of the groups benefited from this this new approach of induction chemotherapy. So this trial called the interlace trial is definitely that something we are all considering and thinking about applying to our patients, turning our to a different trial here. This is called pembrolizumab plus chemo radiotherapy for high risk locally advanced cervical cancer, a randomized double blind phase three trial also nicknamed the 18 study.

00:36:19:16 - 00:36:50:24
Unknown
And it was presented by Dr. Linda Ruska in her group at the annual meeting. So what this is, is a concept of using a new agent immunotherapy agent called pembrolizumab and using it first line for patients undergoing primary chemo radiation. So this trial enrolled over 1000 patients in 30 countries. And what they ultimately demonstrated is when you add this immunotherapy drug called pembrolizumab to the traditional primary chemo radiation, that there is also improved progression free survival.

00:36:50:24 - 00:37:18:19
Unknown
And this is really significant. Interestingly, it did not improve overall survival in the entire population. However, when they look specifically at patients with stage three or four, a disease, they saw improved overall survival. So in this subset of patients, it was particularly beneficial in ultimately the adverse events or side effects were similar between the group that got the immunotherapy drug versus the traditional group.

00:37:18:21 - 00:37:43:21
Unknown
Patient reported outcomes were similar as well. And so basically this data supports the use of pembrolizumab with chemo radiotherapy as a new standard of care for newly diagnosed, previously untreated, high risk, locally advanced cervical cancer patients, and in fact, highlighting yellow FDA approve use of this drug in January of 2024. So here again, you can see how the trial was designed.

00:37:43:21 - 00:38:09:20
Unknown
There are two groups we talked about the new drug versus a traditional with the pembrolizumab Group. You had to continue taking that pembrolizumab for 15 cycles every six weeks. So it is for a long time. But that being said, the benefit is seen here with the progression free survival, the green curve on top with the novel agent certainly did better with less recurrence and less death.

00:38:09:22 - 00:38:38:16
Unknown
And again, that overall survival, while not statistically significant, was beneficial for stage three and four. And here patient report outcomes are basically asking patients on trial about their symptoms, their quality of life and so on, so forth. And basically you can see it summarized in the table that the two groups were about equal. So even getting the additional immunotherapy, they felt, you know, just as well as the group that got the traditional.

00:38:38:16 - 00:39:03:19
Unknown
So that's reassuring here. I wanted to share another study that was highlighted at our annual meeting, and this study is called The Primary Results from BTC, A randomized Phase three Trial. First line Autism is a MAB combined with bevacizumab in a platinum doublet for metastatic persistent recurrent cervical cancer. This was presented by Dr. Okin and and and her group.

00:39:03:21 - 00:39:38:15
Unknown
And so this week nicknaming the beat seek trial. What they were studying is adding tocilizumab, which is also a immunotherapy agent to bevacizumab which is a anti-VEGF agent. And this is a drug that sort of works by inhibiting blood vessel growth in the tumor environment. So when you combine these two drugs plus the traditional chemotherapy that we talked about, paclitaxel, carboplatin, it improves progression free survival, overall survival in patients with recurrent or metastatic cervical cancer.

00:39:38:15 - 00:40:10:02
Unknown
And you can see the progression free survival was improved with the medium of 13 versus ten months and the overall survival was improved as well, with a median of 32 versus 22 months and overall safety profile was very manageable. So the takeaway here is that this new immunotherapy drug atezolizumab, combined with bevacizumab added to platinum based chemotherapy, should be considered as a new first line therapy option for metastatic persistent or recurrent cervical cancer.

00:40:10:04 - 00:40:44:11
Unknown
And this here is a diagram again, showing this particular trial. The patients who were eligible for the trial metastatic persistent recurrent cervical cancer, no prior systemic therapy previously for metastatic or recurrent. And they were randomized to these two groups getting either the novel agents with Atezolizumab, with Bev versus only Bev and Parker Taxol or Carboplatin clabber Platinum. And of course the patients were assessed for recurrence, progression and survival.

00:40:44:13 - 00:41:23:23
Unknown
And here you can see the curves demonstrating the benefit of adding these novel agents. The blue curve on top is that it is Elysium, plus bevacizumab, plus chemo versus the more traditional just bevacizumab plus chemo. And you can see the difference in improved survival with progression free on the left chart and then with overall survival on the right chart, talking about another trial that showed certainly advances in cervical cancer treatment for recurrent metastatic patients.

00:41:24:00 - 00:42:05:16
Unknown
This is the efficacy and safety of two two sodium AB, the Dothan versus investigator's choice of chemotherapy in the second line or third line recurrent or metastatic cervical cancer. It also has some nicknames ANOVA Trial or Georgi 3057 and this is additional data from the Global Randomized Open Label Phase three study. This was presented by Dr. Brian Storm of it's and his group and to so NAB was evaluated in patients with recurrent metastatic cervical cancer who previously received up to two prior lines of therapy, which could include receiving previously bevacizumab and or pembrolizumab the immunotherapy agent.

00:42:05:18 - 00:42:31:23
Unknown
So too soon Mab alone was compared to standard chemotherapy. They enrolled 500 patients. It was a very large study, and they did show that to NAB improved overall survival at the planned interim analysis at 12 months. There are some side effects, including I you know, side effects on the eye as well as neuropathy, numbness in the fingers or toes and some bleeding, but none of them were serious or life threatening.

00:42:32:00 - 00:43:01:21
Unknown
So the takeaway is that two So to NAB is effective in second and third line setting with a median overall survival approximately 12 months and may be considered a potential new standard of care. And so with this data, the FDA under accelerated approval program has this agent approved, approved under the accelerated approval program and is currently under full review by the FDA as of May of 2024, which is very exciting.

00:43:01:23 - 00:43:36:19
Unknown
So what is this agent? So to so NAB is an antibody conjugate that targets tissue factor, which is found on cervical cancer cells and it is this tissue factor is attached to a cytotoxic agent called among E, which basically gets into the cancer cell and basically disrupts their growth and basically allows a cancer cell to be killed. So this is a very novel approach to delivering cancer treatment straight to the cancer cells themselves.

00:43:36:21 - 00:44:23:04
Unknown
And so here you can see the way the trial was designed. It's for women with recurrent or metastatic cervical cancer, meaning they previously already generally receive treatment. But now, unfortunately, the cancer has progressed and they need a newer treatment. And so using this drug versus chemotherapy, they showed that there was an improved survival. And so here the survival curves, again, you can see that overall survival is a curve on the left side using this new drug versus traditional agents, and that there was definitely improvement at 12 months, 48% versus 35 and then progression free, meaning did folks progress or pass?

00:44:23:06 - 00:44:50:19
Unknown
Again, looking at this right graph here with the new drug, 30% versus 18% at six months. So again, statistically improved. And you can see here there are side effects. We have to be very cautious and manage those, but with appropriate management that we can safely get the patients to treatment. Up to 50% do have some type of ocular event, 35% do have some type of neuropathy.

00:44:50:24 - 00:45:18:18
Unknown
But again, generally speaking, these can be safely managed. A couple other trials wanted to speak up briefly here. Presented at the annual meeting efficacy and safety of nine M.W. to eight 2821, which is the antibody drug conjugate lectin for monotherapy drug in patients with recurrent or metastatic cervical cancer. Multicenter open label phase one to study presented at the annual meeting by Dr. Yang in their group.

00:45:18:20 - 00:45:46:06
Unknown
And this is again another novel therapy again ADC. So it's linking like a drug that can get into the cancer cell itself. And specifically for patients who have locally advanced or metastatic cervical cancer, this is still quite early phase and they enrolled 40 patients with a median follow up of about 5 to 6 months. Overall response rate was 40%.

00:45:46:06 - 00:46:12:19
Unknown
This disease control rate was 89%. Again, still very early in the study, but it was overall well-tolerated. So to say there are more and more agents out there that are being investigated that can get straight into the cancer cells themselves to hopefully attack those and be able to to really treat patients hopefully with less other side effects and complications.

00:46:12:21 - 00:46:48:21
Unknown
And here I wanted to highlight another study that received a lot of attention at the annual meeting efficacy and safety of trastuzumab drugs that she can in patients with her two expressing solid tumors, biomarker and subgroup analysis from a cervical endometrium ovarian cancer cohorts. And this study is nicknamed Destiny and it was presented by Dr. Vicky Marker in her group Phase two open label multicenter study targeting tumors that express her to protein, and patients either had two or more power lines of therapy.

00:46:49:02 - 00:47:17:20
Unknown
They enrolled 40 cervical cancer patients. And what was truly impressive was the response rate that I will show you in next few slides. The takeaway is that this new drug, tDCS, is a potential treatment for cervical cancer patients who are heavily pretreated with other medications or even radiation previously, and whose tumor expresses HER2 protein marker. And there was a pretty impressive response rates.

00:47:18:01 - 00:47:52:21
Unknown
So again, this particular drug was studied in multiple cancer populations, including uterine cervix ovary. And you can see the response rates here. They treated 40 patients. You can see in the blue table, which is directed to cervix patients, 20 out of 40 had a response, which is quite good. And for those who really expressed the her to a lot on their tumor tissue, six out of eight meaning 75% of patients had a response, which is actually very high when we're looking at patients who had been treated previously with other agents.

00:47:52:23 - 00:48:20:10
Unknown
So that is very certainly exciting news, even though the sample size was small. So, you know, as we look at where how far we've come over the years, this summary slide from Dr. Terry's presentation at the annual meeting demonstrates that we have certainly seen better agents, newer agents and more improved survival for all our cervical cancer patients. Some of the older trials are listed here looking at cisplatin, plaque attacks on them.

00:48:20:10 - 00:48:51:06
Unknown
Bevacizumab. Then we have this keynote 826 with bevacizumab pembrolizumab, and you can see that the survival has as much improved 24 months, 32 months, etc. And that is very exciting news for first line recurrent metastatic patients and then patients that need additional treatment after that. We have that too. So to Medvedev, which we talked about, as well as other agents such as CEP symmetric lab that are available.

00:48:51:06 - 00:49:20:13
Unknown
So these are all more novel agents, more targeted. And it really is opportunity for our patients here. To summarize, this is a table from the National Comprehensive Cancer Network guidelines. All the agents that we can use now for treating cervical cancer patients. And these are basically all IV agents that are listed on this table. It's a little bit complicated table, but it's to to demonstrate that we are looking at more and more agents now.

00:49:20:13 - 00:49:45:06
Unknown
Currently than we have in the past. And I have maybe one minute left to quickly mention of vaccine therapy. We previously talked about preventive vaccines and now there are more and more studies available looking at therapeutic vaccines, meaning trying to get rid of cancer and get rid of the pre-cancer conditions when it exists. So this is not prevention.

00:49:45:06 - 00:50:10:01
Unknown
This is actually trying to treat the pre-cancer cancer. This was presented by Dr. Levinson at the annual meeting where there's a vaccine that's targeting specifically the HPV virus, the E6 E7 protein within the virus. And for what it's worth, they studied it's early phase study. They were studying patients with actually pre-cancer, what we call dysplasia in patients with dysplasia.

00:50:10:03 - 00:50:38:16
Unknown
And they found that there was a 78% rate of clearance of HPV 16 in these patients with CIN, 2 to 3. So pre-cancer conditions and 2 to 3 and some clearance of other high risk HPV types as well. And this was actually quite interesting that when they looked at the microscopic biopsies at six months, that seven out of nine patients had improvement of their pre-cancer condition.

00:50:38:18 - 00:51:05:14
Unknown
So it's to say that, you know, there is a lot of study out there about using HPV vaccines to try to get rid of the pre-cancer or cancer stage and not just merely prevent it. So in summary, when we talk about cervical cancer, where we at, it's still prevalent in the U.S. and worldwide. And there definitely are racial disparities and social factors that we need to consider when we're thinking about resources and delivering care.

00:51:05:16 - 00:51:31:19
Unknown
That being said, there's also been plenty of advances in this space of how we treat cervical cancer in terms of post surgery, as well as the medications that we use for it. And also though I didn't talk about it, there advances in radiation treatment as well. There are novel therapies and precision medicine that we're applying to cervical cancer patients and we're going to continue studying this to hopefully have even more to offer.

00:51:31:21 - 00:52:09:04
Unknown
And vaccine therapies are also being studied and very exciting in that space. So I thank you for the opportunity to present this talk today and I'm happy to take any questions and I will stop sharing my screen. I think I Eesha you might be unmute. Am I? Can you hear me now? Okay, perfect. All right. Thank you so much for breaking down these findings from Asha.

00:52:09:04 - 00:52:37:06
Unknown
This is super informative, informative, and we really appreciate it. We had several pieces, many questions, a few things you already touched on, but we'll just kind of get through them and if you all still want to submit any questions, feel free and we'll try to get through what we can. Okay. So are there any new updates on immunotherapy specifically?

00:52:37:08 - 00:53:04:00
Unknown
I think now you're muted. Sorry. So, absolutely. There are definitely as as spoken of in the several studies I mentioned, the pembrolizumab, there is also a separate submit the lab. There's the other, you know, immunotherapy agents that are being studied in China. But in the U.S., yes. Pembrolizumab we've seen has been FDA approved initially for a fancy recurrent.

00:53:04:00 - 00:53:26:02
Unknown
And now we're trying to move it up into front line treatment, you know, as was discussed. So I think it's really a huge benefit. It's a huge benefit. And I think patients are having better outcomes. So absolutely awesome. I've heard more people are living with metastatic living longer, with metastatic cervical cancer. Do you know what advances have made this possible?

00:53:26:04 - 00:53:52:07
Unknown
Yeah, So I think it's multiple different types of advances. So in terms of the I.V. medications we talked about, immunotherapy is definitely one of them. In terms of the other like tip deck to certain lab VEDOTIN. Right. That's another very targeted therapy that's getting straight into the cancer cells. So generally not sort of affecting all the other cells of the body, but trying to get straight to the cancer cells.

00:53:52:09 - 00:54:19:06
Unknown
And there's, you know, even radiation therapy, There's more advanced radiation methods. Right. In the old days that the the radiation was not as refined and now we're able to treat now, even if there's a little isolated recurrence, sometimes we can do a tiny bit more radiation SBIR to refine radiation. So it really is a multi combination approach, you know, to being able to really tailor therapy, offer it.

00:54:19:08 - 00:54:40:24
Unknown
And I didn't even mention this in this talk, but in addition, we are able to send tumor out for tumor testing where we say we're going to genomic profile, these tumors rise. We're actually looking very broadly to see if there are any other gene markers. Right. That could be additional targeted agents that I didn't even mention in this talk.

00:54:41:01 - 00:55:14:09
Unknown
But that we're doing in practice. And so I think it really opens the door for opportunity to think about every type of modality of therapy and using combinations for sure. For sure. have there been new developments in radiation for cervical cancer patients? Yes, absolutely. And I think I briefly mentioned some of those newer techniques like SBT, things like that, where it's really and proton therapy is another form of very refined delivery of radiation.

00:55:14:11 - 00:55:40:09
Unknown
And so they're of course, they're used for very specific situations and circumstances. So I think the most important thing is that you would be able to talk with your health care team, you know, in if it were your gynecologic oncologists, your radiation, you know, oncologists or medical oncologists and think about what at what point would be best for what what condition of the cervical cancer journey, as I call it.

00:55:40:11 - 00:56:08:02
Unknown
But absolutely. And I know maybe some centers have some more of these advanced treatment options and others, I think it never hurts to just ask, you know, even if your center didn't have it, you know, maybe are there other centers that may have it available? And sometimes these treatments aren't that long. So there may be an opportunity to say, you know, just for a particular portion of your treatment, you may be able to consider, is that an option for me?

00:56:08:04 - 00:56:32:02
Unknown
And the other thing I would I would say is good to ask about is, you know, sometimes you think, well, would I get there and are there resources to help me? And I think it's always good to ask your health care team and even organizations like Share, you know, maybe there are resources to help patients with travel costs or, you know, any of these other factors that are important to be able to get the care you need.

00:56:32:04 - 00:57:01:14
Unknown
Absolutely Absolutely. Let's see. Have you how can patients keep up with the latest news and updates about cervical cancer treatments? Yeah, great question. So there is so much news out there. Sometimes it's just hard to know where to look. Right. So I think that there are certainly very I mean, of course, asking your health care team number one, right.

00:57:01:14 - 00:57:29:03
Unknown
That that's always a good place to start. But then there are other sources that are certainly very, very informative, reliable So, of course, National Institutes of Health, National Cancer Institute. I think there are plenty of Americans Cancer Society there also foundation and like we mentioned here, Foundation Women's Cancer Society of Gynecologic Oncology has some resources. Patient advocacy groups such as SHARE also are trying to bring that information to the patients.

00:57:29:03 - 00:57:58:23
Unknown
Right? The other things is, for example, even the annual meeting which I spoke of, you know, the Society of Dynamic annual meeting, it is certainly open to patients. And there's actually also, you know, entire day conference that is dedicated to the patient, actually. So I think keeping your eyes open for those are great opportunities and you really get to get in there and learn and share experiences.

00:57:58:23 - 00:58:34:23
Unknown
And I think and it's wonderful, even as a provider, honestly, to hear the experiences of patients. Absolutely. Absolutely. Last question What are you most excited about for the future of cervical cancer treatment? Yeah, I think I think there's just a lot of things that are exciting, you know? And I think that in the old days, you know, people were very cautious and reserved and hesitant about the treatments because there weren't as many treatments.

00:58:34:23 - 00:59:07:00
Unknown
Right. We were more just saying, hey, they're standard radiation and there's maybe one or two or three or four drugs that we have available. Right. But I think in the space that we're at now with precision medicine, like there's just more there's more options, there's more novel agents. And I think what we need to do is we just keep needing to move forward, like we need to think about what are opportunities, How can we bring these novel agents literally from the lab studies to the patients?

00:59:07:00 - 00:59:40:22
Unknown
Right. And ultimately, how can we have patients do better, have a better daily life and and live longer? You know, want to eradicate cervical cancer. Right. Like that. W.H.O. has this huge initiative. It's not just one group or this group or that group. It's literally a worldwide initiative. And we can potentially prevent it as well. Right. So it's it's I think I'm really excited that everyone's actually thinking about it and that that there are newer therapies and and we just want to keep building in this space, right?

00:59:40:22 - 01:00:00:03
Unknown
We really want more opportunities. So I think it's all of the above. Awesome. Well, thank you so much, Dr. Co, for an informative program and thanks to all of you for participating and submitting questions. Please be sure to check out shares, upcoming educational programs and support groups and follow us on social media. Please take a moment to complete the survey.

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Unknown
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