Recent Advances in Cervical Cancer Treatment - Episode 11

Second-Line Immune Checkpoint Inhibition in Metastatic Cervical Cancer

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An overview of second-line immune checkpoint inhibitor use in patients with relapsed or refractory metastatic cervical cancer.


Bradley Monk, MD, FACOG, FACS: I want to conclude second-line checkpoint inhibitors. There is another one, balstilimab, which has been studied and looks promising. It has been filed to the FDA and has an action date, what we call a PDUFA [Prescription Drug User Fee Act] date, of December 16th. There is also cemiplimab. It’s possible that in the second line, we could have 3 checkpoint inhibitors, pembrolizumab, balstilimab, and cemiplimab. Dr Tewari, please tell us about EMPOWER-Cervical-1, why it was done, and what the results are.

Krishnansu S. Tewari, MD: It’s another great collaboration, this one with the GOG [Gynecologic Oncology Group] and ENGOT [European Network for Gynaecological Oncological Trial groups]. When bevacizumab filled an unmet need, it created a new patient population, one that progressed on platinum-based therapy. We needed a second-line option, so we studied this in a phase 3 randomized trial, cemiplimab, an anti–PD-1, versus physician’s choice chemotherapy. We made a list of chemotherapy options that reflected different parts of the world where the study was conducted, and we showed a significant improvement in overall survival in the squamous cell population, which was the first part of our statistical hierarchy, 11 versus 8 months. We also showed with the intention-to-treat population a significant improvement in survival. Although it wasn’t planned or part of the statistical hierarchy, the results with adenocarcinoma were thought provoking. It was a tolerable monotherapy, we didn’t have to combine it with bevacizumab or chemotherapy. Going forward, this is an important option for patients.

Bradley Monk, MD, FACOG, FACS: Dr Pothuri, do we need 3 checkpoint inhibitors in virtually identical populations? It will be interesting to see if cemiplimab or balstilimab gets an all-comer indication. That will create options, particularly with the imperfections associated with PD-1 testing. What are the benefits or the insignificance of having 3 checkpoint inhibitors in the same space?

Bhavana Pothuri, MD: BAL [balstilimab] was studied with ZAL [zalifrelimab], it’s the PD-1 with a CTLA-4, and the response rate with the combination appears to be superior to single agent. That has been shown with the CheckMate 358 trial with IPI/NIVO [ipilimumab, nivolumab], that was presented in 2018 at ESMO [European Society for Medical Oncology annual meeting]. Having the doublet will be important in the treatment of recurrent cervical cancer, and it’s good to have options for patients. Sometimes they tolerate one better than the other, even with a single agent.

Bradley Monk, MD, FACOG, FACS: Dostarlimab is important in MSI [microsatellite-instability]-high endometrial cancer because it’s a path to first line with chemotherapy, shown in the RUBY trial. Balstilimab is important because it’s a path to PD-1/CTLA-4. To date, there’s no sponsor that is doing that. It is an incremental benefit to the combination, but in and of itself, it may not be impactful. There’s another molecule made by the same sponsor called AGEN1181, which is a better CTLA-4. We have next-generation CTLA-4s that are better in the therapeutic index, they have fewer immune-related adverse reactions, but the same dual checkpoint opportunities.

Premal H. Thaker, MD, MS: Hopefully, financially some of the prices might help, especially because these are cancers worldwide. Maybe there will be more beneficial cost ratios in other markets or countries.

Bradley Monk, MD, FACOG, FACS: We have 3 overlapping PARP inhibitor indications in platinum-sensitive maintenance. If you respond to second- or third-line platinum, you give maintenance PARP. At my clinic, my partner was discussing with his nurse practitioner a patient who needed a PARP inhibitor in platinum-sensitive maintenance. He said to give her the one with the lowest co-pay, and I thought that was smart. It matters with PARP inhibitors; checkpoint inhibitors are more similar, but PARP inhibitors are different in price. My vision is that there are foundations that want to help patients, maybe we can in a compliant way, have a foundation or charity pay the co-pay. What do you think of that?

Premal H. Thaker, MD, MS: That would be awesome.

Warner K. Huh, MD, FACOG, FACS: Particularly for the Medicare population.

Bradley Monk, MD, FACOG, FACS: Right. We need to do it so that it’s not viewed as inducement, we need to be compliant, but the health care system is broken, and it’s too costly. Anything that we can do is ideal.

Transcript edited for clarity.