Dr. Bradley Monk, a professor and director of the Division of Gynecologic Oncology at Creighton University School of Medicine St. Joseph’s Hospital and Medical Center in Phoenix, Arizona joins the program to talk about the FDA approval of pembrolizumab (KEYTRUDA) for treatment of patients with recurrent metastatic cervical cancer.
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Dr. Bradley J. Monk is board certified by the American Board of Obstetrics and Gynecology in Obstetrics & Gynecology and Gynecologic Research. Dr. Monk’s specialties – Gynecologic Oncology and the multidisciplinary of prevention and treatment (surgery, radiation, and chemotherapy) of vulvar, vaginal, cervical, uterine, fallopian tube, primary peritoneal and ovarian cancers. He is world famous leader in developing new therapeutic approaches and co-authored more than 230 articles in peer reviewed journals such as New England Journal Medicine, Journal of Clinical Oncology and Clinical Cancer Research.
Neal Howard: Welcome to the program. I’m your host, Neal Howard. Our guest is Dr. Bradley Monk. He’s an oncologist and he’s joining us here on the program today to talk about the recent approval of Merck’s KEYTRUDA®, the recent FDA approval of this drug. Welcome to the program, Dr. Monk. Thank you for taking the time.
Bradley Monk: Thank you, Neal. Thank you for having me. I’m a gynecologic oncologist. Our specialty comes out of OB/GYN. We specialize in gynecologic cancers and I practice in Phoenix, Arizona.
N: Is that what you went into initially when you set out to be a doctor or did something happen in your life to steer you in that direction?
B: I grew up in Arizona. I was struck by the high incidence of cervical cancer here in the Phoenix metropolitan area and as a … I have chaired the NRG Oncology Cervical Cancer Committee for the last 11 years and I’m currently the Chair of the Gynecologic Cancer Intergroup Cervical Cancer Committee. So it’s my pleasure to try to find new medicines and quite frankly to try to prevent these cancers because it continues to be a significant healthcare problem.
N: With that being said, what is the impact healthcare-wise of cervical cancer here in the United States?
B: Cervical cancer is one of the most preventable cancers. We recommend that all boys and girls be immunized against the ideologic virus called the Human Papillomavirus or HPV between the ages of 9 and 12 all boys, all girls and then to be screened with a Pap test and also we can test for the virus on the cervix beginning at age 21. Despite that this is preventable cancer, there’s still more than 10,000 cases and more than 4,000 deaths in the United States annually.
N: So how do you care for someone when they’re in the advanced stages of cervical cancer once they reached that point?
B: Ideally, cancers would be detected at earlier stages where surgery is an option. When surgery is no longer an option, since 1999, it’s a combination of pelvic radiation intracavitary brachytherapy and weekly Cisplatin chemotherapy.
N: That’s every single week you have to go through chemo and I guess once you recover from the chemo it’s time to go again.
B: That’s right. So in the whole paradigm it’s about 6 weeks of external beam radiation, weekly chemotherapy and brachytherapy right to the cervix is generally effective but we unfortunately still see cases of advanced stages and when it’s diagnosed in advanced stages as many happen, many as half of those patients can recur and that’s where most of the deaths occur or happen.
N: There was a recent FDA approval of a new drug from Merck. Let’s talk about this FDA approval and some of the data that led to this approval.
B: Yes. Thank you. So the first-line treatment for recurrent or metastatic cancer is a platinum drug Cisplatin or Carboplatin plus Paclitaxel which we may know as Taxol and the anti-angiogenesis medication Bevacizumab and that FDA approval came in 2014. That was the first and only approval of a targeted therapy but now in June of 2018, once a patient failed Paclitaxel and Bevacizumab, there are no other options. Those patients who on average are only 45 years of age frequently matriarchs and caregivers within the family, ultimately have no options and recently now KEYTRUDA (Pembrolizumab) immunotherapy was approved in that second-line setting.
N: I understand that this is first of its kind as far as this type of therapy is concerned. What makes it so special from other treatments?
B: Well, the special thing is it’s an antibody against the PD-1 checkpoint and again there were no other options. So I’m sorry to say that the response rate is only about 14%. So it’s not like this helps most women but what it does help them, the responses are durable. In fact, 90% of patients who respond lasts for more than 6 months. So this is a new option for patients who have already failed chemotherapy radiation and then first-line metastatic treatment with platinum taxane Bevacizumab.
N: Would you say that this extended treatment option is why it’s very important to doctors, patients and caregivers alike or do you see more research into KEYTRUDA down the road?
B: No, question. This approval is under the accelerated approval mechanisms which means additional confirmatory trials are needed and indeed it’s our goal to add immune checkpoint inhibitors such as KEYTRUDA (Pembrolizumab) earlier lines of therapy where cure rate can even be higher. But when you add it to the end of the line, when patients are already very terminal and very sick, the magnitude of the benefit is not as great as we would expect if we were to use it earlier and that’s where the research is focused.
N: You mentioned that the average age was like 45. Surely, there are some who fall well below that or above that when they could benefit from this drug. Is that a consideration or does one or the other as far as age concerned reduce the effectiveness of it?
B: Yes. So age really has no impact on the effectiveness of KEYTRUDA in this setting. I must note though that patients are only eligible if they express the ligand for the antibody which is PD-L1 and that’s about 80% of patients. So if you have a patient with recurrent cervical cancer, she should be tested using an FDA-approved test to see if the protein is expressed and if it is, she can receive KEYTRUDA and then if she responds, that response will be durable. There are side effects though and the side effects are that it can cause autoimmune disease because that’s what this does. This stimulates the body’s immune system to kill the cancer but if you go too far then the body’s immune system destroys normal cells.
N: Would you say that all, I guess in your opinion, when it comes to all boys and all girls being vaccinated, what do you see as far as when you talk to patients and colleagues about this actually happening? Would you say that most people have latched on to that ideology in the
last 10,15 years or are we still lagging behind in getting awareness out about the importance of this vaccine?
B: Neal, I appreciate you’re … a string on that. So HPV vaccination was approved 12 years ago and the adoption and implementation have been poor and the first thing I said, this is a highly preventable cancer and no one should have cervical cancer because we can be vaccinated against a virus. We can have Pap test to screen for it in its earliest stages. So yes, beyond a doubt, all societies, the pediatricians particularly because these are 9 to 12-year-old boys and girls recommend this and certainly the Cancer Society then the OBGYN Societies recommend this without question.
N: Where can we go and learn some more online about prevention and learn more about Arizona Oncology?
B: Yes. Thank you. So I think we need to talk to doctors. The number one most important factor in a child getting an immunization is the strength of recommendation from his or her doctor. So I think we, as a medical community need to be unified in our voice and in our confidence in HPV vaccination is critical to preventing this and other cancers, right? – Head, neck cancer, anal, vulvar, vaginal cancer as well and certainly the Internet as a resource. Arizona Oncology has a very nice website but I encourage patients to talk to their doctors and your listeners, Neal, your doctors to talk to their patients so that women don’t have to get cervical cancer and that they have an opportunity to prevent it with HPV vaccination.
N: Thanks for joining us today, Dr. Monk.
B: Thank you very much. Thank you.
N: You’ve been listening to Health Professional Radio. I’m your host, Neal Howard. Transcripts and audio of this program are available at hpr.fm and healthprofessionalradio.com.au. You can also subscribe to this podcast on iTunes, listen in and download at SoundCloud and be sure and visit our affiliates page at hpr.fm.