Birrer Assesses Current Challenges in Cervical Cancer

Michael Birrer, MD, PhD

Oncologists continue to face several challenges when it comes to the prevention and treatment of cervical cancer, according to Michael Birrer, MD, PhD.

“Sadly to say, essentially all cervical cancers could be completely eliminated—if we got the vaccine out to everyone,” said Birrer, director, Medical Gynecologic Oncology, Massachusetts General Hospital Cancer Center, professor of Medicine, Harvard Medical School.

Despite the fact that the HPV vaccine is easily available for most of the US population, the vaccination rate in the country is still remarkably low, said Birrer. Moreover, for patients who are diagnosed with the disease, nearly half do not receive the full standard of care treatment, according to a recent study published in Gynecologic Oncology (Robin TP, et al. 2016;143[2]:319-325.)

Amid the many roadblocks in the treatment of cervical cancer, progress is still being made, slowly but surely, with novel immunotherapeutic regimens.

OncLive: Are there any burgeoning advancements on the horizon right now for cervical cancer?

In an interview with OncLive, Birrer discussed both the recent advancements and remaining challenges in the treatment landscape of cervical cancer.Birrer: I can’t say there’s anything definitive in terms of results, but what we’re all anticipating is that it is going to be meaningful, that this is the poster child for immunotherapy. This is an HPV-driven tumor, just like head and neck cancer. The viral antigens are there, and it should really be responsive, or we should at least get disease control using the checkpoint inhibitors.

There is one GOG trial that has gone to completion. It’s a small phase II trial. I’ve only heard rumors that it’s a surprisingly low response rate, but these are tricky trials. If you don’t use immune RECIST, then what you frequently see with patients is that some of their tumor gets smaller, and some of it gets a little bigger. By regular RECIST, that would be progression. But as we know, these immunotherapies can be a little bit tricky, so that trial may be a little hard to interpret.

We personally have anecdotal experience using the drug off-label at Massachusetts General Hospital, in particular in vulvar cancer, which is very similar to cervical cancer, as much of it is HPV-driven. And we’ve had a couple of spectacular responses; inoperable tumors just sort of melt away. So I think that’s exciting, and ultimately, the next step beyond that would be to see if we could combine immune checkpoint inhibitors with antiangiogenic agents, since those are also active in the cervix.

We need to try to come up with a pure biologic treatment for recurrent cervical cancer, where patients don’t have to go through round after round of cisplatin, which we know is active, but it’s not easy to give, and patients don’t like it.

What are some of the main challenges that should be addressed in the next couple of years in cervical cancer?

There’s even some talk about moving the immune checkpoint inhibitors upfront in pre-invasive disease. If you have a patient with CIN 3 or even carcinoma in situ, and give them 1 or 2 cycles of [an immune checkpoint inhibitor], would that save them from conization or hysterectomy? The challenge there, of course, is this is still a curable patient population, so we don’t necessarily want to mess around with it too much. We don’t want to do the wrong thing. Also, a shot of pembrolizumab (Keytruda) is probably $15,000, so the whole proposition is a bit expensive.Sadly to say, essentially all cervical cancers could be completely eliminated—if we got the vaccine out to everyone. And what is remarkable to me is that our vaccination rate in this country is still very low. If you go into third-world nations, it’s low, but we understand that. It’s expensive, and it’s difficult to get it out there. We don’t really have an excuse here in the United States. Luckily, we have the backup with Pap smears, which work fine, but still, we need much better penetration of the population with the HPV vaccine. And that includes boys, which has now been approved. That’ll have a huge effect.

For treatment, we still have this subset of patients who are not operable. They get chemoradiation, and it is quite effective, it clearly cures patients, but there’s a subset of patients whose tumors comes back, and it’s extremely difficult to deal with. A small percentage of those patients are exenteration candidates, and I still think that’s a procedure I’d like to see disappear, because it’s so horrific, regardless of the fact that it can salvage patients. We need to get better therapies for those patients.

A recent study found that less than half of patients with advanced cervical cancer are receiving all 3 of the therapies considered standard of care. Are there women who choose not to undergo all of those treatments?

Finally, unfortunately, there are the patients who develop recurrent metastatic disease. One study shows positive results for a combination regimen with bevacizumab (Avastin), but we need something better for them.From a patient demographic standpoint, the cervical cancer patient population is very skewed toward the minority population. Why is that? It probably has a lot to do with sexual activity, healthcare, and many of these patients probably enter the country already infected. So that makes it a population that’s special in a lot of regards. They tend to be a population of patients that don’t follow up with healthcare very well. So they’re seen, a pre-invasive lesion is found, they’re scheduled for certain follow-ups, and then they’re lost at that follow-up.

We as physicians in the clinic don’t have the infrastructure that we need to specifically address those underserved populations. We need to do something special for them, rather than just say, “Okay, here’s your appointment.” A lot of inner-city hospitals are stressed and overloaded, they have patients lost at follow-up, and next thing they know, those patients are coming in with advanced cancer.

Even then, for a lot of cultural reasons and I think healthcare and insurance issues, when the patients are finally plugged in, they still have a serious problem. They still fall through the cracks because they don’t want to go through chemoradiation, which is not easy, as there are a lot of local toxicities. So for all those reasons, it’s difficult.

Also, let me just say that cervical cancer is viewed, in this country, as a rare tumor, and there’s something to be said about that. There are 8000 cases, about 4800 deaths, but nevertheless, it’s real, and it’s there. But because of that, I think it’s very hard to get industry partners to get interested in it. We use the argument, “Look, they’re real, they’re patients, they need to be treated.” And worldwide, it’s a huge problem. But worldwide, you’re dealing with a lot of countries where they’re not going to be able to develop a drug that will cost $12,000 a month. So those are all the challenges that we see here. It’s sort of a forgotten tumor, unfortunately.