How Systemic Therapy is Combating Advanced CSCC - Episode 5
Neil D. Gross, MD, FACS: At the European Society for Medical Oncology [ESMO] Congress meeting in 2019, the pharmacokinetics were confirmed to be equivalent for 3-week dosing to 2-week dosing with cemiplimab. Certainly it’s easier for patients to get a dose every 3 weeks. Many of these patients are older. It may be cumbersome for them to come into a clinic, or they may have to travel some distance. So it’s great to have an option to be able to dose patients every 3 weeks instead of every 2 weeks. And that 3-week dosing is what we’re incorporating into trials moving forward.
There can be toxicity with treatment with any immunotherapy, and cemiplimab is no different. In the trials that have been presented so far and in our own studies, there’s probably about a 10% rate of immune-related adverse events. These are managed, as with all immune-related adverse events, typically by stopping the medication and frequent use of anti-inflammatories like steroids.
Axel Hauschild, MD: When the study data have been presented in the cohorts—locally advanced and metastatic—and in the fixed-dose schedule of cemiplimab, we were surprised how low the toxicity was. We expected to see more treatment discontinuations because the patients were rather old, 15 years older than the typical metastatic melanoma patients. But this wasn’t the case. Our impression is that there is equal toxicity if not even less. And it’s 10% to 15% grade 3, 4 toxicities. The treatment discontinuation rate is below 10%, and this looks good in this kind of a population.
We all had experience with ipilimumab, which causes colitis. We had experience with pembrolizumab and nivolumab causing colitis, but more thyroiditis and other adverse events. Everybody who was using this drug in the clinical trial was already experienced.
In the dermatology-oncology community, adverse-event management is something that is completely referred to the routine. Therefore, it’s not a problem for us to manage these adverse events. It would be difficult if this is ipilimumab-nivolumab as given for metastatic melanoma patients, because there’s substantially more toxicity, and I would refrain from treating patients who were older than 80 years old with this amount of toxicities. But for conventional programmed cell death protein 1 [PD-1] antibodies, it’s not a problem for everybody who is used to giving drugs of immuno-oncology.
Dirk Schadendorf, MD: Cemiplimab is a newer player in the field, but it’s a checkpoint inhibitor. We have experience with checkpoint inhibitors like pembrolizumab, nivolumab, and others, and everybody who has used PD-1 blockers also has an easy time with cemiplimab because it’s a class effect of adverse effects you can expect. The handling of these drugs is very similar. The safety profile is very similar to what you are used to treating other oncological diseases with. Most of these adverse effects are mild and easy to manage. There are some adverse effects one needs to be aware of. This includes, for example, the thyroid, which is producing hypothyroidism over time, so monitoring the thyroid function and the hormone status are important.
Transcript Edited for Clarity