Recent Advances in Cervical Cancer Treatment - Episode 3
The panel reflects on the current, optimal use of biomarker testing to guide the management of cervical cancer.
Bradley Monk, MD, FACOG, FACS: Dr. Tewari, let’s move on to biomarkers. This first section is about biology, screening, and prevention. You’ve been an advocate of biomarkers, and you have an NIH [National Institutes of Health] grant for biomarkers in cervical cancer. For the practicing clinician, what are the biomarkers that are relevant in treating cervical cancer today?
Krishnansu S. Tewari, MD:For treatment, it’s a matter of looking at patients that need to be treated with immune checkpoint inhibitors. Patients with recurrent or metastatic cervical cancer, we calculate a CPS [combined positive score] for looking at their PD-L1 expression of not just the cancer cells, but also the lymphocytes, and the macrophages. We get a score and that can help guide selection of therapy, especially in the second line. As far as other panel testing, if you want to sequence the entire genome, you could get the tumor mutational burden and immunotherapy. PD-L1 expression is the predominant biomarker that’s used in practice today.
Bradley Monk, MD, FACOG, FACS: We’re going to talk about a phase 3 trial that’s called KEYNOTE-826, where 89% of the patients were combined PD-L1 score greater than 1+. Of those 11% that are negative, many of those are adenocarcinomas, and at least some of them, are TMB high, tumor mutational burden-high, or MSI [microsatellite instability]-high. By the time you take the 89% that are PD-L1 positive, and then add 2-3% of TMB and MSI, Dr. Pothuri, is it worth testing at all? Or do you say there’s so few patients that are biomarker negative, give a checkpoint to everybody?
Bhavana Pothuri, MD: I test because I’ve had some insurance difficulties without having the PD-L1 status to utilize pembrolizumab [Keytruda]. Going forward, given the data from KEYNOTE-826 and the cemiplimab [Libtayo] data, it appears to be efficacious regardless of PD-L1 status. In the future, we’re not going to need to test.
Bradley Monk, MD, FACOG, FACS: Yes, that’s likely. Where we are today, it’s the labeled indication, it’s companion diagnostic, and maybe it will evolve. Dr. Huh or Dr. Thaker, looking at the TCGA [The Cancer Genome Atlas], there were EGF [epidermal growth factor] activating mutations and now there’s data saying that in the small proportion that have EGF-activating mutations, you can use a tyrosine kinase inhibitor and would require next-gen [next generation] sequencing. Do you do that or is it hard to get the medication paid for and it’s just a PD-L1-TMB-MSI world?
Premal H. Thaker, MD, MS: In our recurrent patients for cervical cancer, we are doing commercially acceptable testing. We have next-gen sequencing, and a lot of immunohistochemistry, because to your point, there’s that rare patient that could use neratinib [Nerlynx]. It’s even smaller portions of the pie, but for that 1 patient that you’re seeing in front of you, you can make a huge difference.
Warner K. Huh, MD, FACOG, FACS: Yes, we do the exact same thing. It’s become the standard of care, at least at our institutions, to do next-gen sequencing on essentially every cervical cancer patient, particularly in the recurrent setting. We’re looking for mutations that would put them on a clinical trial whether to taper or match. But I agree with Dr. Thaker, we take a similar approach to that. Is it hard? Yes. But is it worth fighting for? Absolutely. And we’ve seen successes that are notable.
Transcript edited for clarity.