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    ​​​​​ ​​​​​​​​​Transforming Treatment Approach i​​​​n Advanced CSCC with Immunotherapy

    ​​Sponsored by Regeneron and Sanofi

    Dr. Richard Carvajal, Director of Experimental Therapeutics and Director of the Melanoma Service at Columbia University Irving Medical Center, discusses the diagnosis and management of advanced cutaneous squamous cell carcinoma (CSCC), including an immunotherapy treatment option.1 Advanced CSCC encompasses both locally advanced and metastatic stages of the disease.2,3

    Accompanying this article is a compilation of clinical trial patient images associated with an immunotherapy treatment.1,4-6


    This article reflects the thoughts and opinions of Dr. Carvajal. Sanofi and Regeneron had editorial control over the content.

    How often do you see patients with advanced CSCC in your practice? ​

    Early-stage CSCC is an extremely common diagnosis. As this disease is not formally tracked in state or national cancer registries, the exact incidence is not known. However, there are easily one million new cases diagnosed annually in the US, and we see it often in our clinic.2

    While advanced cases are diagnosed less frequently, CSCC can progress quickly.2,7 This is especially true if it wasn’t treated adequately at initial diagnosis; in cases with particular histological characteristics such as the presence of perineural involvement; and in certain clinical scenarios such as in the setting of systemic immunosuppression. Our group typically sees several patients with locally advanced or metastatic CSCC each month.8

    Why is it important to identify which patients with CSCC are at high risk for disease progression?

    Although there are several staging systems available to estimate risk of recurrence and outcomes in CSCC, there is currently no single universally accepted profile for high-risk disease.7,9 Nevertheless, it is important that dermatologists, medical oncologists, and other involved health care providers quickly identify cases they believe are at high risk for disease progression.3,7,9

    The routine monitoring of high-risk patients for locoregional and distant recurrence through dermatologic and/or radiographic surveillance may help identify recurrent disease at an earlier stage when more management options may be available, such as additional surgery, radiation, or systemic therapies.3,7

    Furthermore, it’s important that discussions regarding dermatologic and/or radiographic surveillance occur among a multidisciplinary team of clinicians. I believe that early multidisciplinary management of patients with high-risk CSCC can improve outcomes.3,7

    When is the ideal time for medical oncologists to be engaged in the treatment of advanced CSCC?

    I would strongly advocate for the inclusion of medical oncologists in the care of CSCC at the time high-risk or advanced disease is diagnosed. This includes patients diagnosed with locally advanced or metastatic CSCC, when we must consider a variety of treatment approaches that may include systemic therapies or enrollment in a clinical trial.7

    How has the treatment paradigm changed for patients with advanced CSCC?

    The regulatory approval of the PD-1 (programmed cell death-1) inhibitor LIBTAYO® (cemiplimab-rwlc) armed oncologists with the first approved treatment option for patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Now, instead of doing a third or fourth resection or another round of radiation on a patient with locally advanced CSCC who will not be cured, institution of systemic immunotherapy can be considered.7

    Important Safety Information for LIBTAYO (cemiplimab-rwlc)

    Severe and Fatal Immune-Mediated Adverse Reactions
    Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue at any time after starting treatment. While immune-mediated adverse reactions usually occur during treatment, they can also occur after discontinuation. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Early identification and management are essential to ensuring safe use of PD-1/PD-L1 blocking antibodies. The definition of immune-mediated adverse reactions included the required use of systemic corticosteroids or other immunosuppressants and the absence of a clear alternate etiology. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
    Please see additional Important Safety Information throughout this article and full Prescribing Information.


    Following is a photo gallery of clinical trial patient experiences with LIBTAYO treatment.

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    ​​How has the introduction of LIBTAYO changed the multidisciplinary team (MDT) approach to managing certain cases of advanced CSCC?

    More than ever, it is important that MDTs are brought together earlier in cases of progressing and/or advanced CSCC to determine if surgery and radiation are likely to be curative, and, if not, whether a systemic therapy, such as LIBTAYO, should be considered instead. Each doctor in the patient’s care team has a potential role in making this decision, whether they are dermatologists, head and neck surgeons, radiation oncologists, pathologists, Mohs surgeons, medical oncologists or others.7

    In my own practice, it has been fantastic to see the increasing collaboration among the different specialties over the past five years. We have established a new community where we have the opportunity to discuss what defines advanced cases and how to best manage them.   

    Is age a consideration when prescribing LIBTAYO for a patient?

    Among the patients included in the efficacy analysis of the LIBTAYO pivotal trials, 34% of patients were between 65 to 74 years old and 41% of patients were 75 years or older. There were no overall observed differences in safety or effectiveness between elderly and younger patients treated with LIBTAYO.1

    What is the recommended dosage for LIBTAYO?

    The recommended dosage of LIBTAYO is 350 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.

    Can you elaborate on the dataset that supports the use of LIBTAYO in advanced CSCC? What kind of responses are we seeing?

    LIBTAYO was approved based on data from an open-label, multi-center, non-randomized Phase 2 trial called EMPOWER-CSCC-1 and was further supported by two advanced CSCC cohorts from an open-label, multi-center, non-randomized Phase 1 trial.1

    Both studies excluded patients with autoimmune disease who required systemic therapy with immunosuppressant agents within 5 years; history of solid organ transplant; prior treatment with anti–PD-1/PD-L1–blocking antibodies or other immune checkpoint inhibitor therapy; infection with human immunodeficiency virus, hepatitis B, or hepatitis C; or Eastern Cooperative Oncology Group (ECOG) performance score ≥2.1

    In the trials, 219 patients with metastatic CSCC (nodal or distant) or locally advanced CSCC who were not candidates for curative surgery or curative radiation received either a weight-based 3 mg/kg dose of LIBTAYO every two weeks or a fixed 350 mg dose of LIBTAYO every three weeks via intravenous infusion (IV).1  The major efficacy outcome measures were confirmed overall response rate (ORR), as assessed by independent central review (ICR) and ICR-assessed duration of response (DoR). Additional endpoints included complete response rate, safety and tolerability.1

    To date, these trials offer the largest and most mature prospective clinical dataset in advanced CSCC. Furthermore, responses have shown to be rapid and durable over time.1​​

    Efficacy results for the 137 patients who received the 3mg/kg dose in EMPOWER-CSCC-1 are in the chart below, with a rapid median time to response of 1.9 months (range: 1.7 to 9.1 months) among responding patients based on an open-label, single-arm trial that did not include comparisons to other treatments (first assessment was performed at 8 weeks).1


    efficacyresultschart.png

    Among the 56 patients with metastatic CSCC who received the fixed 350 mg dose every 3 weeks in the EMPOWER-CSCC-1 trial, the ORR was 41% (95% CI: 28%-55%). Furthermore, the median duration of response had not been reached (range 2.1-11.1+ months) and 65% of responders had a DoR of 6 months or greater.2 The median duration of follow-up for this cohort was 8 months.1

    Among the 26 patients (n=16, mCSCC; n=10, laCSCC) in the two advanced CSCC cohorts from the Phase 1 trial, the ORR was 50% (95% CI: 30%-70%) with all responses being partial responses. The median duration of follow-up was 13 months. The median time to response was 1.9 months (range: 1.7 to 7.3 months), and 85% of patients who responded had a DoR of 6 months or greater.1

    Of note, pharmacokinetic analyses showed that LIBTAYO exposures in patients were consistent across the weight-based and fixed-dose treatment groups.1

    What was the safety profile for LIBTAYO in these pivotal trials?

    The safety of LIBTAYO was evaluated in 591 patients with advanced solid malignancies, which included 219 patients with advanced CSCC from EMPOWER-CSCC-1 and the two expansion cohorts from the Phase 1 trial.1

    The most common adverse reactions reported in at least 20% of patients with advanced CSCC were fatigue, rash, diarrhea, musculoskeletal pain, and nausea. The most common Grade 3-4 adverse reactions (≥2%) were cellulitis, anemia, hypertension, pneumonia, musculoskeletal pain, fatigue, pneumonitis, sepsis, skin infection, and hypercalcemia.1

    LIBTAYO was permanently discontinued due to adverse reactions in 8% of patients; adverse reactions resulting in permanent discontinuation were pneumonitis, cough, pneumonia, encephalitis, aseptic meningitis, hepatitis, arthralgia, muscular weakness, neck pain, soft tissue necrosis, complex regional pain syndrome, lethargy, psoriasis, rash maculopapular, proctitis and confusional state.1

    Serious adverse reactions occurred in 35% of patients. Serious adverse reactions that occurred in at least 2% of patients were pneumonitis, cellulitis, sepsis, and pneumonia.1

    Adverse reaction information is in the table below. 1

    adversereactionchart2.png

    Are there updated data for LIBTAYO in advanced CSCC? What do they show?

    Longer-term data from EMPOWER-CSCC-1 were presented at the 2020 American Society of Clinical Oncology (ASCO) virtual meeting. These results showed an ORR of 46% (95% CI: 39%-53%) following treatment with LIBTAYO, with a median time to response of 2 months (interquartile range: 2-4 months) across the three treatment groups, which were metastatic CSCC and locally advanced CSCC dosed at 3mg/kg every 2 weeks and metastatic CSCC dosed at 350mg every 3 weeks. The median time to CR was 11 months (interquartile range: 7.4-14.8 months) among those who achieved a CR in any group. The median DoR had yet to be reached for any treatment group (range for groups combined: 1.9-34.3 months).4,10

    Updated response rates are in the table below. 4,10

    adversereactionchart2.png


    ​What were the safety findings for LIBTAYO in the longer-term data presented at ASCO 2020?

    Safety was generally consistent with previous data. The most common adverse reactions reported were fatigue (35%), diarrhea (28%) and nausea (24%). The most common Grade 3 or higher adverse reactions were pneumonitis (3%), autoimmune hepatitis (2%), anemia, colitis and diarrhea (each 1%). 

    Adverse reaction information is in the table below.10


    seconadversereactons.jpg

    Important Safety Information

    Warnings and Precautions

    Severe and Fatal Immune-Mediated Adverse Reactions

    Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue at any time after starting treatment. While immune-mediated adverse reactions usually occur during treatment, they can also occur after discontinuation. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Early identification and management are essential to ensuring safe use of PD-1/PD-L1– blocking antibodies. The definition of immune-mediated adverse reactions included the required use of systemic corticosteroids or other immunosuppressants and the absence of a clear alternate etiology. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
     
    No dose reduction for LIBTAYO is recommended. In general, withhold LIBTAYO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue LIBTAYO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated adverse reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids. 

    Withhold or permanently discontinue LIBTAYO depending on severity. In general, if LIBTAYO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids. 

    Immune-mediated pneumonitis: LIBTAYO can cause immune-mediated pneumonitis. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.2% (26/810) of patients receiving LIBTAYO, including Grade 4 (0.5%), Grade 3 (0.5%), and Grade 2 (2.1%). Pneumonitis led to permanent discontinuation in 1.4% of patients and withholding of LIBTAYO in 2.1% of patients. Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in 58% of the 26 patients. Of the 17 patients in whom LIBTAYO was withheld, 9 reinitiated after symptom improvement; of these, 3/9 (33%) had recurrence of pneumonitis. Withhold LIBTAYO for Grade 2, and permanently discontinue for Grade 3 or 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids. 

    Immune-mediated colitis: LIBTAYO can cause immune-mediated colitis. The primary component of immune-mediated colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory immune-mediated colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2.2% (18/810) of patients receiving LIBTAYO, including Grade 3 (0.9%) and Grade 2 (1.1%). Colitis led to permanent discontinuation in 0.4% of patients and withholding of LIBTAYO in 1.5% of patients. Systemic corticosteroids were required in all patients with colitis. Colitis resolved in 39% of the 18 patients. Of the 12 patients in whom LIBTAYO was withheld, 4 reinitiated LIBTAYO after symptom improvement; of these, 3/4 (75%) had recurrence. Withhold LIBTAYO for Grade 2 or 3, and permanently discontinue for Grade 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids. 

    Immune-mediated hepatitis: LIBTAYO can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2% (16/810) of patients receiving LIBTAYO, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (1.4%), and Grade 2 (0.2%). Hepatitis led to permanent discontinuation of LIBTAYO in 1.2% of patients and withholding of LIBTAYO in 0.5% of patients. Systemic corticosteroids were required in all patients with hepatitis. Additional immunosuppression with mycophenolate was required in 19% (3/16) of these patients. Hepatitis resolved in 50% of the 16 patients. Of the 5 patients in whom LIBTAYO was withheld, 3 reinitiated LIBTAYO after symptom improvement; of these, none had recurrence.

    For hepatitis with no tumor involvement of the liver: Withhold LIBTAYO if AST or ALT increases to more than 3 and up to 8 times the upper limit of normal (ULN) or if total bilirubin increases to more than 1.5 and up to 3 times the ULN. Permanently discontinue LIBTAYO if AST or ALT increases to more than 8 times the ULN or total bilirubin increases to more than 3 times the ULN. 

    For hepatitis with tumor involvement of the liver: Withhold LIBTAYO if baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN. Also, withhold LIBTAYO if baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN. Permanently discontinue LIBTAYO if AST or ALT increases to more than 10 times ULN or if total bilirubin increases to more than 3 times ULN. If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue LIBTAYO based on recommendations for hepatitis with no liver involvement. 

    Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

    Immune-mediated endocrinopathies: For Grade 3 or 4 endocrinopathies, withhold until clinically stable or permanently discontinue depending on severity. 

    • ​Adrenal insufficiency: LIBTAYO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold LIBTAYO depending on severity. Adrenal insufficiency occurred in 0.4% (3/810) of patients receiving LIBTAYO, including Grade 3 (0.4%). Adrenal insufficiency led to permanent discontinuation of LIBTAYO in 1 (0.1%) patient. LIBTAYO was not withheld in any patient due to adrenal insufficiency. Systemic corticosteroids were required in all patients with adrenal insufficiency; of these, 67% (2/3) remained on systemic corticosteroids. Adrenal insufficiency had not resolved in any patient at the time of data cutoff 
    • Hypophysitis: LIBTAYO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue depending on severity. Hypophysitis occurred in 0.4% (3/810) of patients receiving LIBTAYO, including Grade 3 (0.2%) and Grade 2 (0.1%) adverse reactions. Hypophysitis led to permanent discontinuation of LIBTAYO in 1 (0.1%) patient and withholding of LIBTAYO in 1 (0.1%) patient. Systemic corticosteroids were required in 67% (2/3) of patients with hypophysitis. Hypophysitis had not resolved in any patient at the time of data cutoff 
    • Thyroid disorders: LIBTAYO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue LIBTAYO depending on severity 
    • Thyroiditis: Thyroiditis occurred in 0.6% (5/810) of patients receiving LIBTAYO, including Grade 2 (0.2%) adverse reactions. No patient discontinued LIBTAYO due to thyroiditis. Thyroiditis led to withholding of LIBTAYO in 1 patient. Systemic corticosteroids were not required in any patient with thyroiditis. Thyroiditis had not resolved in any patient at the time of data cutoff. Blood thyroid stimulating hormone increased and blood thyroid stimulating hormone decreased have also been reported 
    • ​​Hyperthyroidism: Hyperthyroidism occurred in 3.2% (26/810) of patients receiving LIBTAYO, including Grade 2 (0.9%). No patient discontinued treatment and LIBTAYO was withheld in 0.5% of patients due to hyperthyroidism. Systemic corticosteroids were required in 3.8% (1/26) of patients. Hyperthyroidism resolvedin 50% of 26 patients. Of the 4 patients in whom LIBTAYO was withheld for hyperthyroidism, 2 patients reinitiated LIBTAYO after symptom improvement; of these, none had recurrence of hyperthyroidism 
    • Hypothyroidism: Hypothyroidism occurred in 7% (60/810) of patients receiving LIBTAYO, including Grade 2 (6%). Hypothyroidism led to permanent discontinuation of LIBTAYO in 1 (0.1%) patient. Hypothyroidism led to withholding of LIBTAYO in 1.1% of patients. Systemic corticosteroids were not required in any patient with hypothyroidism. Hypothyroidism resolved in 8.3% of the 60 patients. Majority of the patients with hypothyroidism required long-term thyroid hormone replacement. Of the 9 patients in whom LIBTAYO was withheld for hypothyroidism, 1 reinitiated LIBTAYO after symptom improvement; 1 required ongoing hormone replacement therapy
    • Type 1 diabetes mellitus, which can present with diabetic ketoacidosis: Monitor for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold LIBTAYO depending on severity. Type 1 diabetes mellitus occurred in 0.1% (1/810) of patients, including Grade 4 (0.1%). No patient discontinued treatment due to type 1 diabetes mellitus. Type 1 diabetes mellitus led to withholding of LIBTAYO in 0.1% of patients

    Immune-mediated nephritis with renal dysfunction: LIBTAYO can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.6% (5/810) of patients receiving LIBTAYO, including fatal (0.1%), Grade 3 (0.1%), and Grade 2 (0.4%). Nephritis led to permanent discontinuation in 0.1% of patients and withholding of LIBTAYO in 0.4% of patients. Systemic corticosteroids were required in all patients with nephritis. Nephritis resolved in 80% of the 5 patients. Of the 3 patients in whom LIBTAYO was withheld, 2 reinitiated LIBTAYO after symptom improvement; of these, none had recurrence. Withhold LIBTAYO for Grade 2 or 3 increased blood creatinine, and permanently discontinue for Grade 4 increased blood creatinine. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids. 

    Immune-mediated dermatologic adverse reactions: LIBTAYO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1–blocking antibodies. Immune-mediated dermatologic adverse reactions occurred in 1.6% (13/810) of patients receiving LIBTAYO, including Grade 3 (0.9%) and Grade 2 (0.6%). Immune-mediated dermatologic adverse reactions led to permanent discontinuation in 0.1% of patients and withholding of LIBTAYO in 1.4% of patients. Systemic corticosteroids were required in all patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 69% of the 13 patients. Of the 11 patients in whom LIBTAYO was withheld for dermatologic adverse reactions, 7 reinitiated LIBTAYO after symptom improvement; of these, 43% (3/7) had recurrence of the dermatologic adverse reaction. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold LIBTAYO for suspected SJS, TEN, or DRESS. Permanently discontinue LIBTAYO for confirmed SJS, TEN, or DRESS. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids. 

    Other immune-mediated adverse reactions: The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% in 810 patients who received LIBTAYO or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions. 

    • Cardiac/Vascular: Myocarditis, pericarditis, and vasculitis. Permanently discontinue for Grades 2, 3, or 4 myocarditis
    • Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, and autoimmune neuropathy. Withhold for Grade 2 neurological toxicities and permanently discontinue for Grades 3 or 4 neurological toxicities. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids 
    • Ocular: Uveitis, iritis, and other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss 
    • Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis, stomatitis 
    • Musculoskeletal and connective tissue: Myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica 
    • Endocrine: Hypoparathyroidism 
    • Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection

    Infusion-related reactions 
    Severe infusion-related reactions (Grade 3) occurred in 0.1% of patients receiving LIBTAYO as a single agent. Monitor patients for signs and symptoms of infusion-related reactions. The most common symptoms of infusion-related reaction were nausea, pyrexia, rash, and dyspnea. Interrupt or slow the rate of infusion for Grade 1 or 2, and permanently discontinue for Grade 3 or 4. 

    Complications of allogeneic HSCT 
    Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT. 

    Embryo-fetal toxicity
    LIBTAYO can cause fetal harm when administered to a pregnant woman due to an increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LIBTAYO and for at least 4 months after the last dose.

    Adverse reactions
    • In the pooled safety analysis of 810 patients, the most common adverse reactions (≥15%) with LIBTAYO were musculoskeletal pain, fatigue, rash, and diarrhea 
    • In the pooled safety analysis of 810 patients, the most common Grade 3-4 laboratory abnormalities (≥2%) with LIBTAYO were lymphopenia, hyponatremia, hypophosphatemia, increased aspartate aminotransferase, anemia, and hyperkalemia  

    Use in specific populations 

    • Lactation: Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO 
    • Females and males of reproductive potential: Verify pregnancy status in females of reproductive potential prior to initiating LIBTAYO 

    Please click here​ for full Prescribing Information​.  

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    References:

    1. LIBTAYO® (cemiplimab-rwlc) injection full U.S. prescribing information. Regeneron Pharmaceuticals, Inc., and sanofi-aventis U.S. LLC. Available at: https://www.regeneron.com/sites/default/files/Libtayo_FPI.pdf

    2. Mansouri B, Housewright C. The treatment of actinic keratoses—the rule rather than the exception. J Am Acad Dermatol 2017; 153(11):1200. doi:10.1001/jamadermatol.2017.3395.

    3. Schmults CD, et al. High-Risk Cutaneous Squamous Cell Carcinoma A Practical Guide for Patient Management. Springer. ISBN 978-3-662-47081-7 (eBook). DOI 10.1007/978-3-662-47081-7.

    4. Data on File. Regeneron Pharmaceuticals Inc. 2020.

    5. Data on File. Regeneron Pharmaceuticals Inc. 2018.

    6. Migden M, Rischin D, Schmults C, Guminski A, Hauschild A, Lewis K et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. New England Journal of Medicine. 2018;379(4):341-351.

    7. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Squamous Cell Skin Cancer V.2.2020. National Comprehensive Cancer Network, Inc. 2020.

    8. Califano JA, Lydiatt WM, Nehal KS, et al. Cutaneous squamous cell carcinoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. Springer; 2017:171-181.

    9. Jennings L, Schmults CD. Management of high-risk cutaneous squamous cell carcinoma. J Clin Aesthet Dermatol. 2010;3(4):39-48.

    10. Rischin D, Khushalani NI, Schmults CD, et al. Phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC): longer follow-up. Poster presented at: American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program; May 29-31, 2020.


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