Cemiplimab-rwlc Approved by FDA for Advanced Basal Cell Carcinoma
Posted: Thursday, February 11, 2021
Commentary by Karl D. Lewis, MD, Non-melanoma Skin Cancer Site Editor for JNCCN 360
Associate Professor, Division of Medical Oncology, University of Colorado Denver School of Medicine
Approval of Cemiplimab-rwlc for Squamous Cell and Basal Cell Carcinomas
The approval of cemiplimab-rwlc to treat advanced cutaneous squamous cell carcinoma was a major breakthrough. Prior to cemiplimab’s approval, there was no systemic therapy specifically indicated for patients with this devastating disease. Clinicians would generally use cytotoxic chemotherapy, but this was associated with limited efficacy and often significant side effects. Using a PD-1 antibody/immunotherapy approach has proven to result in meaningful response rates and a durable benefit in a significant number of patients. Longer follow-up of this cohort of patients confirms the durability of these responses.
The approval of cemiplimab is also a major development in the treatment of patients with locally advanced or metastatic basal cell carcinoma. Although targeted therapy with Hedgehog inhibitors has been associated with significant response rates in this disease, these drugs are difficult for most patients to tolerate long term due to their side effects. In addition, patients can have primary or secondary resistance to these agents. Cemiplimab has demonstrated a meaningful response rate in the locally advanced basal cell carcinoma cohort, and these responses seem to be durable, consistent with immune responses seen in other cutaneous malignancies, such as melanoma and squamous cell carcinoma. Although the results for the metastatic cohort are based on an interim analysis, with the response rate of 21% and all responders maintaining the response for at least 6 months, there is reason to be optimistic that these results will hold up with longer follow-up.
On February 9, the U.S. Food and Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for patients with locally advanced and metastatic basal cell carcinomas. The approval is indicated for patients who had been previously treated with a Hedgehog pathway inhibitor or for whom a Hedgehog pathway inhibitor was not appropriate.
Cemiplimab-rwlc is a monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells. In 2019, it was approved in the European Union for advanced cutaneous squamous cell carcinoma. The recommended dosage of cemiplimab-rwlc is 350 mg as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.
The FDA approval was based on the ongoing, open-label, multicenter, nonrandomized Study 1620 trial. The clinical trial enrolled patients with either locally advanced or metastatic basal cell carcinoma. Patients with locally advanced basal cell carcinoma also had to be ineligible for curative surgery or curative radiation therapy. These patients had to have experienced disease progression on Hedgehog pathway inhibitor therapy, not achieved an objective response after 9 months of therapy or were intolerant to therapy. Every patient received 350 mg of cemiplimab-rwlc every 3 weeks for up to 93 weeks until disease progression, unacceptable toxicity, or completion of planned treatment.
A total of 84 patients with locally advanced basal cell had an overall response rate of 29%. About 79% of responders maintained their response for at least 6 months. Among 28 patients with metastatic basal cell carcinoma, the overall response rate was 21%, and all responders maintained their responses for at least 6 months.
Severe adverse reactions to cemiplimab-rwlc included pneumonitis, hepatitis, colitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus and nephritis, and infusion reactions. The most common adverse reactions observed in 20% or more patients were fatigue, musculoskeletal pain, diarrhea, rash, and pruritus.
For full prescribing information, visit accessdata.fda.gov.
Disclosure: Dr. Lewis has received honoraria from Incyte and Array BioPharma; received research funding from Roche, Merck, Incyte, Array BioPharma, Nektar, Iovance Biotherapeutics, and Bristol Myers Squibb; and served as a consultant or advisor to Array BioPharma, Merck, Roche, and Regeneron Pharmaceuticals.