A key opinion leader explores the significance of biomarkers, including PD-L1 CPS score, TMB, MSI, and HER2, in shaping advanced treatment strategies for cervical cancer patients, emphasizing personalized care and clinical trial opportunities.
Ramez N. Eskander, MD: It is incredibly exciting to talk about cervical cancer, specifically biomarkers informing treatment. Not long ago we were not informed to the degree that we are today, and we didn’t understand the particular relevance of biomarkers in informing cervical cancer therapy. So what do I mean by that? Initially, [I mean] our understanding of the relevance of the PD-L1 CPS, or combined positive score. Why is that relevant? Because we know that there is a therapeutic strategy for which there’s a companion diagnostic. I’m alluding to the approval of pembrolizumab based on the KEYNOTE-158 trial that gave us the opportunity for immune checkpoint inhibition in cervical cancer based on the biomarker of the PD-L1 CPS score.
So, in clinical practice for us, we get a PD-L1 CPS score institutionally in-house. That’s a 22C3 IHC [immunohistochemistry] companion diagnostic that we have available for cervical cancer patients and we know whether they would be a candidate. Now, whether you do that on the initial biopsy or whether you wait until the patient has a recurrence to do that, [is] a bit variable based on practice, institution, and practice setting. But I am of the mindset of understanding the biology of the tumor. We’ll talk about various biomarkers [that help] inform our treatment opportunity and strategy.
What other biomarkers are relevant in cervical cancer? Although uncommon, you may have cervical cancers that are tumor mutational burden high and/or MSI [microsatellite instability] high. And those cervical cancers that are TMB high or MSI high may also allow for a patient to respond to immunotherapy based on disease site, agnostic drug approvals of immune checkpoint inhibition in TMB high or MSI high solid malignancies. So again, a therapeutic treatment paradigm that will improve outcomes for our patients. In the cervical cancer space, we’re also looking at HER2. We understand that the frequency of HER2 aberrations is not high. But we’ve also seen data that suggest a response to anti-HER2 directed therapies in the cervical cancer patient population, most recently the DESTINY-PanTumor-02 abstract that was presented at ASCO [American Society of Clinical Oncology Annual Meeting] in 2023 [that] really highlighted the therapeutic benefit of trastuzumab deruxtecan. It’s an antibody-drug conjugate with a target of HER2 in IHC 2+ plus or 3+. We’re not going from an in situ hybridization-based assay, but rather IHC 2+ or 3+ showing a provocative signal in those patients with trastuzumab deruxtecan.
As a therapeutic strategy for our patients who may not have [other] treatment options, IHC may be informative to guide use of such an agent to try to elicit benefit. And of course, if there is a clinical trial for which a patient would be eligible based on biomarker testing, that’s relevant and important for us to explore and discover so that patients can be offered treatment on trial if they’re not responding to standard of care therapies. That is a problem that we face with patients who have recurrent disease progressing on prior treatment.
For us, we do in-house, as I mentioned, PD-L1 CPS. But in the same breath, we also send tumors out for comprehensive molecular testing. And that’s done with commercial labs. There are many different commercial labs that can be used in order to inform molecular alterations or aberrations that may help guide treatment…. And whether that’s done again at diagnosis or at recurrence can vary, and it depends on the stage. If I have a patient who presents with metastatic disease at diagnosis, I will almost always perform comprehensive molecular testing because [those] data [are] incredibly informative for me. If I have a patient who has very early-stage disease amenable to surgical resection with a high cure rate, we may not [do the testing] at that point in time and wait in the event that the patient has a recurrence. And whether or not a patient is getting treated with chemoradiation for locally advanced disease, again, this is a more individualized decision, but I am of the mindset of having [those] data early on to help inform my patient’s counseling and management if they develop a recurrence, if beneficial.
Transcript is AI generated and edited for readability.