Metastatic Cervical Cancer: Moving Immune Checkpoint Inhibition to the Front Line


Panelists reflect on the potential for immune checkpoint inhibition to become a frontline option in metastatic cervical cancer, and what that means for the second-line setting.


Bradley Monk, MD, FACOG, FACS: Dr Huh, there will be a day where if you don’t get checkpoint inhibitors with chemotherapy and radiation, the CALLA and KEYNOTE-A18 trials, then you’ll get it with the KEYNOTE-826 trial. The number of patients who will get to second line to receive pembrolizumab, balstilimab or cemiplimab is going away. How long will it take, both for the United States and internationally?

Warner K. Huh, MD, FACOG, FACS: You’re asking how long it will take these patients to see one?

Bradley Monk, MD, FACOG, FACS: Yes. At some point, because checkpoint inhibitors don’t work after checkpoint inhibitors, the number of patients in the second line who are checkpoint naїve will be zero. How long will it take to arrive at that situation?

Warner K. Huh, MD, FACOG, FACS: It could be as fast as 2 to 3 years in the United States. For the rest of the world, it is much longer because of the cost equipoise, but it could be as short as 3 years in the United States.

Krishnansu S. Tewari, MD: I think it’s going to be less than a year in the United States.

Bradley Monk, MD, FACOG, FACS: But it takes time to recur, right?

Krishnansu S. Tewari, MD: But once you get KEYNOTE-826, I’m talking about in the first line.

Bradley Monk, MD, FACOG, FACS: I get it, let’s say you get KEYNOTE-826, half of the patients…. But I agree with both of you.

Krishnansu S. Tewari, MD: If they adopt KEYNOTE-826, and they should, they’re going to adopt it right away.

Bradley Monk, MD, FACOG, FACS: Will there be countries that say it’s better to do sequential therapy? Even today in Canada, the GOG-0218 trial regimen is not approved. The way you get bevacizumab in ovarian cancer is a trial, platinum-resistant recurrent ovarian cancer. Do you think some countries will not pay for it in first line, but pay for checkpoint in the second line, via cemiplimab?

Krishnansu S. Tewari, MD: I don’t think so, not with the survival benefit. Bevacizumab in ovarian cancer is different.

Bradley Monk, MD, FACOG, FACS: What do you think, Dr Thaker?

Premal H. Thaker, MD, MS: I agree. I think patients will jump on this. You’re not going to have that issue of sequential treatment.

Bhavana Pothuri, MD: The addition of the CTLA-4 may overcome the lack of efficacy with single-agent checkpoint. The BLA [Biologics License Application] for that is through Project Orbis, for BAL/ZAL [balstilimab, zalifrelimab]. We should receive wide adoption if it’s approved.

Bradley Monk, MD, FACOG, FACS: I want your help to get PD-1, CTLA-4, TIGIT [T-cell immunoreceptor with immunoglobulin and ITIM domain], or a VEGF in the front line with chemotherapy and radiation. It’s all about curing patients. We introduce drugs to the market in later line, we go earlier in combinations, and then obviously other tumor types.

Bhavana Pothuri, MD: What about utilizing checkpoint inhibitors as adjuvant therapy after radical hysterectomy?

Bradley Monk, MD, FACOG, FACS: Someone said the failure rate is low, and radical hysterectomies are becoming less common. We have something, like the OUTBACK trial, but if you have positive nodes after radical hysterectomy. I’m prepared to predict that study will be negative, it’s an historical SWOG [Cancer Research Network] study.

Transcript edited for clarity.

Related Videos
Michael J. Birrer, MD, PhD
Bhavana Pothuri, MD
Alessandro Santin, MD
Bhavana Pothuri, MD
Megan Hitchins, PhD
Megan Hitchins, PhD
Related Content