Case 3: Practical Management of Metastatic CSCC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Ahmad Tarhini, MD, PhD:It would be interesting now to discuss the immune-related adverse events with immune checkpoint inhibitors. Dr Wong, would you like to discuss the expectations in terms of autoimmune toxicities with cemiplimab?

Deborah J. Wong, MD, PhD:In contrast with cytotoxic chemotherapy and targeted therapies, the adverse-effect profile of immunotherapies is quite distinct. In general, we may see fewer serious adverse effects, not so many cytopenias. The most common adverse effects with immunotherapies include some mild fatigue, but generally not to the point where patients are debilitated or unable to complete their activities of daily living. Commonly we can see some nausea. Again, most of the time patients are not requiring any severe antiemetic therapy. There are autoimmune adverse effects resulting from immune activation. The most common ones can be skin rash, and that is generally quite easy to manage with topical steroids. There could also be thyroid dysfunction, so either hypothyroidism or hyperthyroidism.

In general, the adverse-effect profile is very mild and very manageable. Of course, with immunotherapies, there is a possibility for very serious—even life-threatening—adverse effects. We need to be keyed in to evaluate for any autoimmune activation—pneumonitis, colitis, hepatitis, and so forth. Again, those tend to be much less common, and if they occur, they tend to be quite easy to manage by stopping the immune therapy and instituting immune suppressants such as steroids.

Ahmad Tarhini, MD, PhD:Thank you, Dr Wong. Dr McKean, you discussed how you monitor these patients in terms of blood testing, pretreatment, and so on. How about patient education and communication with patients during this treatment?

Meredith McKean, MD:I usually outline a time of consent with patients and expectations. Now that we have a very good understanding of what we as medical oncologists are monitoring for, I think it’s always great to inform the patient. This is because if a patient has initial onset of diarrhea, if they notify your office, you can take prompt management. It’s the patients that come in weeks later who are severely dehydrated and have additional complications from their toxicities. It’s important to let patients know that there can be very serious toxicities. But as soon as they know if there are any symptoms, they should call us, let us know, and come into the office, because these are generally easily managed with the information provided.

Ahmad Tarhini, MD, PhD:Close communication is very important. They have to call us if they have any symptoms or are not feeling well. That’s what we stress.

Meredith McKean, MD:Correct.

Deborah J. Wong, MD, PhD:I think it’s also important to make your colleagues in other subspecialties aware of the unique adverse-effect profile of these immune therapies. If a patient is presenting to the emergency department with dehydration from diarrhea, the emergency department physician needs to be aware of the possibility of autoimmune colitis as opposed to what they may normally think about as diarrhea related to chemotherapy.

Ahmad Tarhini, MD, PhD:Some places have started an immune-related adverse-event board where different subspecialties get together and discuss, which is obviously unique and again stresses the importance of the multidisciplinary approach to managing those toxicities.

Deborah J. Wong, MD, PhD:Uh-huh.

Ahmad Tarhini, MD, PhD:Building on your discussion, Dr Wong, the phase II study in theNew England Journal of Medicinereported in terms of grade 3 or more adverse events, in about 42% of patients, 29% were considered serious, and 5% led to discontinuation of treatment. These are probably the most serious ones that leads to discontinuation. There were 5% of events that actually led to an outcome of death and again stresses what we all know about the importance of close communication—catching these toxicities early on and initiating management.

What was interesting in ASCO [the American Society of Clinical Oncology Annual Meeting] of this year is the update, the 12-month follow-up in 59 patients. This is now a median follow-up of about 60.5 months. The overall response rate was 49.2%, and 10 patients achieved a complete response, which is about 17%, and 19 patients a partial response, which is about 32%. This again speaks to the durability of responses with immune therapy as compared with chemotherapy, where we see actually benefits erode over time. With immunotherapy we see durability and maintaining the same level of benefits.

In terms of progression-free survival, it was interesting in the presentation at ASCO this year that the median progression-free survival was actually 18.4 months as well, and this speaks to the durability of these responses. The median overall survival was not reached, although at 24 months about 70.6% of patients were still alive in the study at 2 years, which are exciting data.

As a take-home message, our first-line treatment for patients with metastatic, inoperable cutaneous squamous cell carcinoma is anti—PD-1 [programmed cell death protein 1] immunotherapy. We have FDA approval for cemiplimab. The response rates are exciting, upward of 50%. Most of these responses are durable. Immune-related adverse events are very important to keep in the back of our mind and in the discussion with our patients, stressing close communication between the clinic and the patient in managing these toxicities and involving a multidisciplinary approach in managing toxicities the way we plan the treatment for the patients.

Transcript edited for clarity.