Novel Immune Checkpoint Inhibitors in Advanced Cervix Cancer - Episode 6
David M. O’Malley, MD, discusses the management of adverse events across various regimens for cervical cancer treatment and provides insight on future directions for disease management.
David M. O’Malley, MD: When we talk about adverse events with I/O [immuno-oncology] therapy, it’s important to have a high degree of suspicion. This isn’t just checking the CBC [complete blood count] and making sure their ANC [absolute neutrophil count] is OK. Obviously, we have a high degree of suspicion with pneumonitis. We don’t have a blood test for pneumonitis. We also consider colitis, making sure we’re asking them if they’re having diarrhea. It’s important to think about the endocrinopathies that will also sometimes present with vague symptoms or frontal headache, severe fatigue, and maybe even present like sepsis. You have to think about it at any point during therapy.
How does that contrast to the adverse effects of tisotumab vedotin? TV [tisotumab vedotin] is an antibody-drug conjugate. When we look at the 3 main toxicities of TV [tisotumab vedotin], No. 1 is eye toxicity. No. 2 is bleeding, but it’s really just epistaxis. It’s not dangerous bleeding, but it can be annoying epistaxis. And third is neuropathy, with the payload of antimicrotubulin that we see some neuropathy. Manage that as you manage neuropathy with paclitaxel.
However, a new toxicity that some of us have seen is eye toxicity with TV [tisotumab vedotin]. The eye toxicity can be mitigated by using interventions proactively. What are some of the things? We tell patients, “Don’t do things that are going to irritate your conjunctiva.” Avoid wearing contact lenses. Use lubricating eye drops throughout the entire process. Around the time of the infusion, use steroid eye drops as well as constrictors to minimize the delivery to the conjunctiva. We also do eye packs over the eyes. That has the same rationale. If you have a patient who develops conjunctivitis, make sure you have partnered with an ophthalmologist who can help you treat these symptoms. The mitigation strategies have significantly decreased the occurrence of grade 3 or higher conjunctivitis. But they can continue to be a low-grade process, which can be drastically mitigated by partnering with an ophthalmologist.
The future of recurrent cervical cancer and treatment revolves around improving the chance for curative intent. One of the best ways to do that is through dual blockade from an immune standpoint. We also have other drugs being developed that are exciting with regard to molecular basis and antibody-drug conjugates. It’s so important for us to enroll these patients on clinical trials if that’s an option. We need to move the field forward as we’ve done over the last 10 years and continue to see improvements in not only how long patients are living but also their quality of life, potentially increasing curative intent.
My advice for the treatment of women with recurrent or metastatic cervical cancer is to use your best therapies up front. We know that when we utilize our best therapies—platinum doublets, antivascular therapy with bevacizumab, immunotherapy with pembrolizumab—patients do better and live longer. And this is in randomized controlled trials. Obviously, PD-L1 testing continues to be important. The option for first-line therapy to add pembrolizumab to your treatment regimen of platinum doublet plus bevacizumab are for those who have a CPS [combined positive score] score of 1 or higher. It’s very important to check the PD-L1 status right away.
Transcript Edited for Clarity