Ramez N. Eskander, MD, explores evolving treatment options, including immunotherapy and antibody drug conjugates, in recurrent cervical cancer, highlighting the importance of biomarkers and clinical trials in this dynamic landscape.
Ramez N. Eskander, MD: In the context of the advancements that we’ve had in the front line…platinum, taxane, pembrolizumab with or without bevacizumab if you’re PD-L1 positive [based on] CPS [combined positive score] companion diagnosis, [or] platinum, paclitaxel, bevacizumab if you’re negative—that’s clearly impacted what we do in the second line. Why? Because whether…a patient’s been exposed to immune checkpoint inhibition is relevant. This is an evolving time. It’s a dynamic time. These approvals are recent, so there may be patients who were treated in the frontline metastatic setting with chemotherapy and bevacizumab and did not receive immunotherapy. In those patients, if they have a positive PD-L1 CPS…then they would be candidates for single-agent pembrolizumab. And that’s based on the accelerated approval from the KEYNOTE 158 trial.
In addition, if they’re biomarker positive, if they’re TMB [tumor mutational burden] high or MSI [microsatellite instability]-high, they would be candidates for immune checkpoint [therapy] based on the disease site agnostic FDA approval. So, in the recurrent setting, if someone was checkpoint naïve, then they have an opportunity to be treated with immune checkpoint inhibition. Of course, there are other opportunities for therapy. We will speak about opportunities for antibody-drug conjugates in this space, specifically tisotumab vedotin. There are opportunities for clinical trials in this space in the recurrent setting, and there are opportunities for alternate chemotherapeutic treatment strategies. We talk about pemetrexed as a single agent, we talk about gemcitabine as a single agent, we talk about topotecan.
But I will say response rates to those single agents are quite modest. And that was seen in our prospective phase 3 trials like the cemiplimab phase 3 trial, where response rates to physician’s choice chemo[therapy] in that cohort when compared to checkpoint was 6%. So again, it humbles us to realize that standard-of-care options with chemotherapy, cytotoxic chemotherapy, in the record setting has very modest benefits. And that’s what makes us so passionate about understanding biomarkers, informing treatment, but also continuing to drive clinical trial and drug development.
And I will just expand on this a little bit…if in the front line a patient was treated with a platinum-based combination and immune checkpoint inhibition, with or without bevacizumab, then re-treating [that patient] with immune checkpoint inhibition is an unknown arena, meaning we don’t have strong data informing the benefit of re-treatment with an immune checkpoint inhibitor in those patients, particularly if they progressed while on an immune checkpoint inhibitor. And that’s why in that patient population…it’s quite relevant to understand the data behind the antibody-drug conjugate tisotumab vedotin as a therapeutic treatment opportunity.
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