Libtayo (cemiplimab-rwlc, pronounced seh-MIP-lih-mab) is a type of drug known as a human monoclonal antibody. It targets the immune checkpoint receptor PD-1 (programmed cell death protein-1) and has become the standard of care for some forms of metastatic cutaneous squamous cell carcinoma (CSCC) over the last 18 months, and has shown promise in treating other cancers, too. Libtayo acts on a cellular pathway known as PD-1, blocking it and allowing the immune system to recognize and fight cancer cells. Since its approval, tests conducted on other cancers that use the same pathway have yielded promise. Those include the more common basal cell carcinoma, and non-small-cell lung cancer. Libtayo won U.S. Food and Drug Administration (FDA) approval in September 2018 for those with metastatic or locally advanced cancers who are not candidates for curative surgery or radiation. With four thousand prescriptions written since then, the drug has successfully halted or reversed CSCC for some patients with no other viable treatment options, doing so with few or minor side effects relatively quickly. “We generally know within two or three months if we will get a benefit from Libtayo,” says Svetomir N. Markovic, MD, PhD, an oncologist at Mayo Clinic in Minneapolis, who frequently uses the medication. So far, the drug’s effects have been enduring. “Our follow-up in our trials shows cancers maintaining or improving two or three years out,” says Daren Kwok, spokesman for the U.S.-based Regeneron, one of the drug’s codevelopers. Roughly 95 percent of CSCC cases are curable by tumor removal. Treatments are less effective when CSCC invades deeper skin layers (“advanced” CSCC) and when it spreads to other areas (“metastatic” CSCC). CSCC claims 15,000 lives a year in the United States, according to the Skin Cancer Foundation (SCF). (6) The disease is among the few malignancies not registered in the cancer research database. It affects between 800,000 and one million people, as detailed at a December 2018 OncLive conference. A study published in the Journal of the American Academy of Dermatology projected 700,000 new diagnoses annually, with numbers increasing as the population ages. (5) Before Libtayo dominated CSCC treatment, few drugs were effective for cases that did not respond to tumor removal. “There were some medications being used off-label, but their response rates were pretty low,” says Emily S. Ruiz, MD, MPH, director of the High-Risk Skin Cancer Clinic at Dana Farber and Brigham and Women’s Cancer Center in Boston. “This drug has definitely changed the landscape for those patients,” Dr. Ruiz says. In clinical trials, Libtayo achieved an almost 50 percent response rate for metastatic CSCC, as reported by Regeneron Sanofi Genzyme. More than four million cases of basal cell cancer are diagnosed each year in the United States, most believed due to sun exposure. In addition, the non-small-cell cancer accounts for at least 80 percent of lung cancers, according to the American Cancer Society. Regeneron and Sanofi report on the Libtayo website that serious adverse reactions occurred in about 28 percent of patients, resulting in a halt to the medication in 5 percent of all patients. The most common nonserious reactions were fatigue, rash, and diarrhea. (1) Other adverse reactions can include:
Immune-mediated pneumonitis (inflammation of the lungs, which can lead to coughing or shortness of breath)Immune-mediated colitisImmune-mediated hepatitisImmune-mediated endocrinopathies, including adrenal insufficiency, hypophysis, hypothyroidism, hyperthyroidism, and type 1 diabetesImmune-mediated nephritis with renal dysfunctionImmune-mediated dermatologic reactionOther neurological, ocular, gastrointestinal, musculoskeletal, and connective tissue reactions, and hematological side effects (1)
Because Libtayo can cause the immune system to attack normal organs and tissues in any area of the body, each patient must undergo blood work periodically while taking the drug to track liver and thyroid function. Other side effects, such as diarrhea or abdominal pain, may not be detected via blood tests. It is important that patients report all symptoms and changes to their doctor. (1) Libtayo should not be used by pregnant women as it can harm a fetus. Lactating women should wait four weeks after the medication is discontinued before breastfeeding. (1) A total of 108 patients (75 with metastatic disease and 33 with locally advanced disease) were included in the evaluation. The patients received 3 milligram per kilogram (mg/kg) of Libtayo via intravenous infusion every two weeks over a 48-week period. Treatment continued until either tumor growth was arrested, a reaction caused the patient to discontinue the medication, or the planned treatment was completed. Patient responses were evaluated every eight weeks. At the conclusion, nearly one-half of the participants — 47.2 percent — experienced partial shrinkage or complete disappearance of their tumors. Tumors did not regrow immediately following the clinical trials. Avoiding the sun, using effective sunscreens, and eschewing tanning beds are the best preventions, particularly if initiated early in life and practiced consistently. Those who are fair-skinned, work outdoors, live in the southern and central United States, or are geriatric are likelier to develop CSCC. “The incidence is increasing, with the number of skin cancer patients over 65 now reaching an all-time high,” says Ruiz. Libtayo is a much-needed addition to the treatment arsenal, say both Ruiz and Dr. Markovic. “CSCC is a rare disease. The medical community went and asked whether treatments similar to those used in melanoma could work here too,” Markovic says. “Fortunately, the answer was ‘yes,’ and there were companies willing to make the investment to study this.”
