In an interview, John Diaz, MD, discusses updates to the cervical cancer treatment landscape and where the field is moving to potentially eradicate this disease in the United States.
While cervical cancer is a serious disease that affects approximately 14,000 women each year, it is a disease that could be potentially eliminated due to effective screening techniques and widespread vaccination against human papillomavirus (HPV), according to John Diaz, MD.
The cervical cancer treatment landscape has evolved in the past decade with the addition of bevacizumab (Avastin) and antibody-drug conjugates to chemotherapy and pembrolizumab (Keytruda), and antibody-drug conjugates. The field continues to make strides and push boundaries with the development of minimally-invasive techniques and robotic surgery.
However, it is important to take precautions prior to a patient's diagnosis of cervical cancer. A key evaluation method includes pap smears as they play a crucial role in detecting any abnormalities in cervical cells and identifying HPV infections early. By also providing the HPV vaccine before exposure to the virus, cervical cancer has a chance to be prevented.
Not only does the vaccine prevent cancer in women, but it can also protect males and females from a variety of other cancers, including head and neck cancers, associated with HPV.
“The take-home message definitely is through screening and vaccination, we should be able to eliminate cervical cancer in the United States and across the world,” said Diaz, chief of gynecologic oncology, for Baptist Health South Florida, in an interview with Targeted OncologyTM.
In the interview, Diaz discusses updates to the cervical cancer treatment landscape and where the field is moving to potentially eradicate this disease in the United States.
Targeted Oncology: For patients who develop cervical cancer, how has their prognosis improved over the past few years?
Diaz: Cervical cancer in the United States and in the developed world has become less common, and that's because of the effective screening that we have with the use of pap smears and HPV screening, we can diagnose these cancers, either in a precancerous lesion, or an early stage where they're treatable and potentially curable. Over the last 5 to 10 years, it's been an exciting time in the treatment of cervical cancer. We've had new medications that have improved the outcomes for our patients. It's been an exciting time to treat women with cervical cancer, and their prognosis has significantly improved over these last 5 to 10 years.
Can you highlight some of those important improvements that we've seen in the past decade?
Cervical cancer treatment has changed dramatically over the last 10 years. In the past, we didn't have a lot of effective treatments. Cervical cancer in the early-stage can usually be treated by surgery alone. The challenge was in those patients when it came back as recurrence, or those women who were diagnosed with metastatic disease at the time of diagnosis. We had limited effective treatment options for them. But that's changed over the last 5 to 10 years.
It started with using a combination of chemotherapies. These were drugs that were platinum-based combinations that improved the outcomes for these patients. We then added an additional medication called bevacizumab. It's an immunotherapy and it targets the VEGF pathway. We looked at women who had either metastatic disease or who had their cancer come back. By adding this medication, this improved their outcomes, so it became the new standard for women to be treated with chemotherapy in addition with this new immunotherapy, bevacizumab. That only continues to improve.
Cervical cancer is often caused by the HPV vaccine, so there's an immune response. It made it interesting to look to see if immunotherapy drugs like checkpoint inhibitors could improve those outcomes. In fact, we saw that as single agents, immunotherapy drugs were effective. We combined them with our traditional chemotherapies and it was even more effective. We just recently had a trial that looked at using combined chemotherapy, and the investigators were allowed to use bevacizumab, which we have shown in the past to improve outcomes. About 75% of women in this trial did use bevacizumab. We then added another immunotherapy, this immune checkpoint inhibitor called pembrolizumab, and we saw an improvement in response rates. We saw an improvement in survival and this has become the new standard for patients with cervical cancer.
We look at these women's cancers and we look to see if they have a [combined positive score] that indicates they would respond to immunotherapy. If they do, and most of the women that have cervical cancer do, we then add this medication. It has changed the landscape for women with cervical cancer. We're excited about this, and we may have a chance for the first time for women with advanced disease to look at a cure with a combination of these 4 medications.
What ongoing research has caught your eye or is particularly exciting in this space.
Equally exciting in the treatment of cervical cancer is we have a new class of drugs. They're called antibody-drug conjugates. A lot of times I'll describe this to my patients as this kind of Trojan horse. These drugs usually bind to a receptor on the cell of the cancer that will then be brought into the cancer cell where they then deliver their payload. There's a medication called tisotumab vedotin [Tivdak], and it's the first antibody-drug conjugate that was approved for the treatment of women with gynecologic cancer, specifically those with cervical cancer. This medication was studied for women who had previously used chemotherapy and their cancer came back. It was comparing traditional chemotherapy with this new drug.
We found that the response rates of this medication and the survival with this was improved compared with traditional chemotherapies. Response rates are still only about 25% with this medication, but it's certainly better than we had seen before with chemotherapy. With this new class of drugs, it's exciting. They have different [adverse] effects profiles. One of the things that people are starting to understand is that with antibody-drug conjugates, there's a risk of ocular toxicities, so it can impact the eye, which is different than we've seen before for both the treating physicians and the patients. The reality is, less than 3% of women on a clinical trial suffered a significant eye toxicity from this. It's an exciting new drug that we now have for the treatment of cervical cancer and we are starting to move this up. Right now we have recurrence, but we're looking at using this medication in combination with bevacizumab and moving it up to the frontline treatment to see if we can get even better outcomes than we currently have. It's an exciting time for the management of cervical cancer.
What are some of the ways to prevent cervical cancer in the United States?
Cervical cancer is not very common in the United States. Thankfully, there are only about 14,000 new cases a year. The reason is we have effective screening for cervical cancer. This is a disease we could potentially eradicate in the United States. The way we do this is through screenings. [It is important] for women to get their pap smears to screen for any abnormalities in the cell and to screen for HPV infection.
The other way we can do this is by, before exposure to HPV, to provide young boys and young girls vaccination against HPV. There's an HPV vaccine that helps prevent you getting exposed to HPV, and the idea is to vaccinate both boys and girls. The reason being is most cervical cancers are associated with HPV, but there are also many cancers that can affect men, such as head and neck cancers, for which there is no screening and is also impacted by HPV. By vaccinating both boys and girls, we can decrease through herd immunity. It can be beneficial to men and prevent HPV-related cancers. If we utilize that strategy of screening and vaccination, we can eliminate this disease here in the United States.
Can you explain robotic surgery for this type of cancer and some of the new technologies and advances seen in this space?
Robotic surgery is minimally-invasive surgery. It's laparoscopy, but instead of the surgeon holding the laparoscopic instruments, the robot holds the instruments and the surgeon controls those instruments. It allows for precision. It allows us to do complicated surgeries through small incisions and those robot arms move just like our arms doing surgery. Robotic surgery has been widely adopted for the treatment of many cancers. Specifically in gynecology, we use it as standard of care now for endometrial cancer, and we're using it for cervical cancer. There was a trial a few years ago called the LACC trial [NCT00614211] that looked at minimally-invasive surgery for the treatment of cervical cancer. That trial demonstrated that those women who underwent a minimally-invasive approach had a worse outcome than women who underwent a traditional open approach. That kind of put the brakes on using minimally-invasive and robotic surgery in the treatment of this disease.
Since that time, we have analyzed this data. We've seen other institutional data to try and determine and better understand why in this 1 specific disease we've seen these outcomes when in other disease sites like uterine cancer, colon cancer, or bladder cancer, laparoscopy or robotics is often used with improvements in patients and surely not a worst outcome. When we decide or look at a couple of different things, we think that tumor size may have an impact on the exposure of the cavity during the removal of the specimen and be part of it. We've now developed different techniques for containment when performing the surgery. An ongoing trial is now comparing open surgery to robotic surgery to see if we can better understand this because we feel that there is a role with these modified techniques to allow women all the benefits of robotic surgery without having a worse oncology outcome. This additional clinical trial will look at trying to answer this question.
Where do you foresee the cervical cancer field moving in the next year?
We've talked a lot about some of the new medications that we have, including the immunotherapy with bevacizumab, pembrolizumab, and there are other immunotherapies that we're looking at, and now this new class of drugs, antibody-drug conjugates. I think what we'll see and what we're looking at with new clinical trials is using a combination of those medications and using the combination of immunotherapy with these antibody-drug conjugates to see if we can get improved outcomes.
We know when we use chemotherapy alone that it's good, but it's not great, so we can improve on that. It's an exciting time as we take these medications from second- or third-line up to the frontline and see if we get better results with these drugs than we can with traditional chemotherapy. I think the future is bright with cervical cancer. The most important thing we can do to prevent it is with pap smears, with HPV vaccination, and again, we can eliminate this disease here in the United States, and hopefully across the world where cervical cancer still is 1 of the most common gynecologic cancers.
It is an exciting time for the treatment of cervical cancer. We have these new medications, particularly the first antibody-drug conjugate for the treatment of gynecologic cancers. We're looking again to see what the role of robotic surgery can be in the treatment of this disease. But the take home message definitely is through screening and vaccination, we should be able to eliminate cervical cancer in the United States and across the world.