Novel Immune Checkpoint Inhibitors in Advanced Cervix Cancer - Episode 5
Dr David M. O’Malley comments on emerging agents in the pipeline for the treatment of recurrent/metastatic cervical cancer and shares his approach to the sequencing of therapies.
David M. O’Malley, MD: As we look at this next generation of cervical cancer therapy, immunotherapy is the key moving forward, and combination immunotherapy is so important. Should it be a PD-1 inhibitor plus the CTLA4, LAG3, or TIGIT? I hope we explore all 3 dual-blockade options. An interesting agent is tiragolumab, which is a TIGIT antibody, most recently combined with PD-1 inhibitor atezolizumab. The SKYSCRAPER-04 trial has completed enrolling patients with previously treated recurrent cervical cancer. I hope we’ll see those results shortly. Once again, dual blockade is key in moving the field forward, potentially curing more patients.
Another agent on the horizon for the treatment of recurrent cervical cancer is cemiplimab. We’ve recently seen the EMPOWER-Lung 1 trial reported. In EMPOWER, we had patients who had previously been treated with a platinum doublet with or without bevacizumab then randomized to cemiplimab, a PD-1 inhibitor, vs physician’s choice, 1 of 5 agents. We found that there’s overall and progression-free survival benefit of cemiplimab. We hope to bring this agent into our armamentarium of therapies, moving beyond just pembrolizumab. What did this trial show me? It reiterated that if we have patients who haven’t previously received I/O [immuno-oncology] therapy in the first line, those patients’ first option should be to move to an I/O PD-1 inhibitor. It’s important in our opportunities to have sustained, durable responses in our patients with recurrent cervical cancer.
I can’t believe that I have the opportunity to talk about sequencing patients with recurrent cervical cancer and metastatic cervical cancer. What an amazing opportunity in the last 5 years. Clearly, in my mind, patients with recurrent metastatic disease should be offered the best therapies available, meaning a platinum doublet—carboplatin or cisplatin, depending on their prior therapies—plus paclitaxel combined with bevacizumab, the antivascular therapy, combined in the first-line setting with pembrolizumab. In those patients, we’re seeing additive benefits without additional toxicities. We need to use our best therapies in our first-line setting. Many of our patients might not have had an eye on the up-front setting.
In the second-line setting, my first option is an I/O treatment. Pembrolizumab is approved, and we suspect we’ll see cemiplimab. Clearly the first choice for all these patients should be clinical trial. What else do we have available? We have 4 or 5 agents that we can use that aren’t exciting, but we do have 1 exciting agent that’s just been approved: tisotumab vedotin. If I had to say tisotumab vedotin all day, I’d be in trouble, so I’m going to call it TV [tisotumab vedotin]. Many of us are calling it TV [tisotumab vedotin]. Response rates are between 25% and 30% as a single agent. If they’ve had previous I/O, my next choice is TV [tisotumab vedotin]. After that, you can pick 1 of 4 to 5 agents. The overall response rate is in the single digits, less than 10%.
Transcript Edited for Clarity