Dr. Axel Hauschild, professor of dermatology and head of the dermato-oncology department at the University Hospital of Kiel in Germany, discusses the recent FDA approval of cemiplimab, a PD-1 antibody treatment for patients with metastatic or locally advanced cutaneous squamous cell carcinomas.

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TRANSCRIPT

[MUSIC PLAYING] Welcome to the Recent Approvals episode of the ASCO University Weekly Podcast. My name is Axel Hauschild. I'm a professor of dermatology and head of dermato-oncology at the University Hospital of Kiel in Germany. Today, we will discuss the approval of cemiplimab, a new PD-1 antibody for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas. As a background to today's discussion, immune checkpoint inhibitors are active therapies in patients with other cutaneous malignancies, like melanomas and mucosal carcinomas already. So far, chemotherapy was given as a routine for patients with advanced or metastatic cutaneous malignancies, and occasionally, cetuximab, an EGFR inhibitor. However, in almost all of these patients, the responses were short-lasting. The analysis of the tumor mutational burden indicated a high sensitivity of more or less all UV-induced cutaneous malignancy for immune checkpoint inhibitors. Therefore, theoretically, cutaneous squamous cell carcinomas are ideal tumors for the treatment with PD-1 or PD-ligand 1 antibodies. On September 28 of 2018, cemiplimab was approved by the FDA for the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas who are not candidate for curative surgery or curative radiation. These data led to the approval of a flat dose of 350 milligrams cemiplimab infused over 30 minutes every three weeks. The approval of cemiplimab was based on a high number of clinically meaningful and durable objective responses observed in patients with two different clinical trials. The results have already been published in 2018, in June, in the New England Journal of Medicine. Both clinical trials were non-randomized, multicenter studies in patients for whom surgery or irradiation was not recommended. Among 108 patients with advanced cutaneous squamous cell carcinomas, including 75 metastatic patients, the overall response rate was 47%, with 4% complete and 44% partial responses. There were no significant differences in the response rate between patients with metastatic and those with locally advanced disease. The median response duration was not reached. And 61% of the responses were durable for six months or longer. Response rates and durability results were consistent across the advanced squamous cell carcinoma subtypes. For patients with locally advanced cutaneous squamous cell carcinomas, the radiographic response rate correlated with clinically relevant shrinkage of visible and often disfiguring tumors demonstrated in the photographic data obtained in these clinical trials. Safety data were evaluable from 434 patients who received cemiplimab in both clinical trials. Serious adverse events were typically immune-mediated, such as colitis or pulmonitis. And in some patients, infusion reactions were observed. The most common adverse events were fatigue, rash, and diarrhea. The treatment discontinuation rate was 12%. The approval of cemiplimab marks a significant advancement in the treatment of patients with metastatic or locally advanced cutaneous squamous cell carcinomas. Cemiplimab is considered as a new standard of care in these patients, since not only an impressive response rate of almost 50%, but also durable responses were observed. As mentioned before, previously, chemotherapies and cetuximab have been used for these patients with limited efficacy, particularly because most responses were only short-lasting. Important to mention is that the approval is not going along with a biomarker test, such as the measurement of PD-ligand 1 expression. Therefore, cemiplimab can be used for all comers with metastatic or locally advanced cutaneous squamous cell carcinomas. So far, there are no data available when cemiplimab has been combined with other agents or irradiation. Also, data from the adjuvant of PD-1 antibodies in high-risk cutaneous squamous cell carcinoma patients are outstanding. However, clinical trials on cemiplimab and other PD-1 antibodies are already planned. In conclusion, cemiplimab adds significantly to the success story of PD-1 and PD-ligand 1 antibodies in cutaneous malignancies. The approval of cemiplimab for cutaneous squamous cell carcinomas leads to changes in the current guidelines for this tumor. Thank you very much for listening to this week's episode of the ASCO University Weekly Podcast. For more information on immune therapy and the treatment of cutaneous squamous cell carcinomas, visit the comprehensive eLearning Center at university.asco.org. [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.