Anna C. Pavlick, DO, a medical oncologist at Weill Cornell Medicine, discusses common and uncommon adverse effects (AEs) with cemiplimab (Libtayo) in patients with cutaneous squamous cell carcinoma.

Cemiplimab, like many PD-1 agents, causes inflammatory AEs, which is one of the most common toxicities, says Pavlick. Among these inflammatory conditions, patients can experience dermatitis, hepatitis, thyroiditis, nephritis, and colitis. Many times, these toxicities are not dose limiting and do not require patients to come off of therapy, notes Pavlick. The most common AE is rash and itching; this effect can be very bothersome for patients because sometimes they will itch, but not have a rash, which could result in some confusion. That is an AE that patients need to be aware of and report because it can be managed, says Pavlick.

Colitis and diarrhea are observed very infrequently with cemiplimab. PD-1 agents are metabolized through the liver and kidneys, so some patients can see some drug-induced hepatitis or nephritis; this is especially true for older patients. Therefore, it is important to keep a close eye on them to ensure their labs are checked before they receive an infusion of cemiplimab. Endocrinopathies are not very commonly reported, however, patients do develop hypothyroidism. That toxicity is easy to monitor because thyroid function tests should be checked every time the patient receives an infusion, adds Pavlick.

While the agent is generally well tolerated, patients do need to understand that if they develop endocrinopathies, 99% of the time they are permanent, notes Pavlick. If a patient develops hypothyroidism and is given levothyroxine (Synthroid) for thyroid replacement, they are going to have to take that drug for the remainder of their life, concludes Pavlick.

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Anna C. Pavlick, DO, discusses common and uncommon adverse effects with cemiplimab in patients with cutaneous squamous cell carcinoma.

Dr. Pavlick on the Safety Profile of Cemiplimab in CSCC

Anna C. Pavlick, DO, professor in the Department of Medicine and Ronald O. Perelman Department of Dermatology, as well as the director of High Reliability Organization Initiatives and the co-director of the Melanoma Program at NYU Langone Health’s Perlmutter Cancer Center, discusses updated results from the COLUMBUS trial in metastatic melanoma.

In the phase 3 COLUMBUS trial, investigators examined next-generation BRAF and MEK inhibitors, says Pavlick. Specifically, they looked at encorafenib (Braftovi) in combination with binimetinib (Mektovi) versus vemurafenib (Zelboraf) or encorafenib alone in patients with advanced BRAF V600-mutant melanoma. With a median follow-up of 16.6 months (95% CI, 14.8-16.9), the median progression-free survival was 14.9 months (95% CI 11.0-18.5) in the combination arm and 7.3 months (5.6-8.2) in the vemurafenib arm (HR, 0.54; 95% CI 0.41-0.71; two-sided 

First, vemurafenib and cobimetinib (Cotellic) emerged in the melanoma treatment landscape back in 2011, and then the next generation was trametinib (Mekinist) and dabrafenib (Tafinlar) in 2013, Pavlick adds. Now, the field has encorafenib and binimetinib, concludes Pavlick.

Anna C. Pavlick, DO, discusses updated results from the COLUMBUS trial in metastatic melanoma.

Dr. Pavlick on the COLUMBUS Trial in Metastatic Melanoma

Anna C. Pavlick, DO, professor in the Department of Medicine and Ronald O. Perelman Department of Dermatology, as well as the director of High Reliability Organization Initiatives and the co-director of the Melanoma Program at NYU Langone Health’s Perlmutter Cancer Center, discusses sequencing challenges faced in the treatment of patients with 

Treatment decisions for patients with melanoma depend upon whether a genetic mutation is present, says Pavlick. Fifty percent of patients with metastatic melanoma harbor a 

 mutation, for which there are targeted agents available, explains Pavlick. Patients with 

 mutations can either receive targeted therapy or immunotherapy, and those without mutations are offered immunotherapy, according to Pavlick.

A current challenge when treating patients with 

-mutant melanoma is determining whether immunotherapy or targeted therapy should be administered first, says Pavlick. Immunotherapy will take some time to work; therefore, if a patient with a BRAF mutation is not doing well, they will likely receive targeted drugs first. Meanwhile, a patient with more indolent disease who looks and feels well will likely receive immunotherapy, concludes Pavlick.

Anna C. Pavlick, DO, discusses sequencing challenges faced in the treatment of patients with BRAF-mutant melanoma.

Dr. Pavlick on Sequencing Challenges in BRAF-Mutant Melanoma Treatment

Anna C. Pavlick, DO, professor in the Department of Medicine and Ronald O. Perelman Department of Dermatology, as well as the director of High Reliability Organization Initiatives and co-director of the Melanoma Program at NYU Langone Health Perlmutter Cancer Center, discusses the importance of immunotherapy for patients with metastatic melanoma.

Immunotherapy has become the focus of research in melanoma. Immunotherapy can help harness a patient’s immune system and attack cancer cells, says Pavlick. Over the last 10 years, the field has seen an improvement in outcomes with the use of immunotherapy.

Whether a patient receives a BRAF inhibitor or does not, immunotherapy is a choice because patients with a BRAF mutation can respond just as well to treatment as patients who do not have the mutation. Immunotherapy has become a cornerstone of melanoma therapy. The field is looking to build on the progress that has been made to make responses better in order to cure more patients, concludes Pavlick.

Anna C. Pavlick, DO, discusses the importance of immunotherapy for patients with metastatic melanoma.
 

Dr. Pavlick on Importance of Immunotherapy in Metastatic Melanoma

Anna C. Pavlick, DO, associate professor of hematology and medical oncology and medical director of the Clinical Trials Office at the Perlmutter Cancer Center at NYU Langone Medical Center, discusses the need for adjuvant immunotherapy in patients with high-risk melanoma.

These are patients who have stage IIb to IIIc or resected stage IV melanoma, Pavlick explains. These are patients in which clinicians are concerned with disease recurrence. Interferon, she adds, was the standard adjuvant treatment for many years, but now researchers are able to use the CTLA-4 inhibitor ipilimumab (Yervoy, which has been FDA approved to use in the adjuvant setting for patients with stage III disease.

Participating in clinical trials will ultimately change the therapeutic options that can be offered for patients and will also lower their risk of developing metastatic disease.

Dr. Pavlick on Adjuvant Immunotherapy in High-risk Melanoma

Anna C. Pavlick, DO, medical oncologist, NYU Langone School of Medicine, discusses ongoing clinical trials exploring treatment with immunotherapy in patients with basal cell carcinoma as well as squamous cell carcinoma of the skin.

Frontline therapy for patients with basal cell carcinoma are hedgehog inhibitors, Pavlick explains. However, similar to the targeted therapies available for patients with melanoma, most patients do become resistant to these therapies. Therefore, since these patients are not chemotherapy-sensitive or radiation therapy-sensitive, a clinical trial is opening in the near future that will explore treatment with immunotherapy for those who fail on hedgehog inhibitors. If the results are promising, this could lead to a new frontline treatment option for these individuals.

Similar to squamous cell skin cancer, Pavlick says there is another clinical trial opening that will explore immunotherapy in this patient population, as well. This would be practice changing for the field, she explains.

Anna C. Pavlick, DO, medical oncologist, NYU Langone School of Medicine, discusses ongoing clinical trials exploring treatment with immunotherapy in patients with basal cell carcinoma as well as squamous cell carcinoma.

Dr. Pavlick on Immunotherapy Clinical Trials in Basal and Squamous Cell Carcinomas

Anna C. Pavlick, DO, associate professor, Hematology and Medical Oncology, medical director, Clinical Trials Office, Perlmutter Cancer Center at NYU Langone, discusses a phase II trial exploring low-dose cyclophosphamide and ipilimumab in metastatic melanoma.

Pavlick says it has been observed in the lab that the T regulatory cells can be regulated when melanoma cells are given low doses of cyclophosphamide. A down-regulation of these cells usually enhances an immune response.

In this phase II trial, patients were given low-dose of cyclophosphamide before receiving a checkpoint blockade with CTLA-4, Pavlick says. Researchers expected to see an enhanced immune response along with a better patient response compared to when patients receive CTLA-4 alone. However, Pavlick says, while the low-dose cyclophosphamide clearly regulated a facet of the immune system, patients’ disease became more refractory to immunotherapy.

Pavlick says the toxicity also increased in these patients. In this study, researchers saw a doubling in toxicities such as, diarrhea, rash, and itching and endocrinopathies compared with ipilimumab alone.

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Anna C. Pavlick, DO

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