LIBTAYO® (cemiplimab-rwlc) is indicated for the treatment of patients with locally advanced basal cell carcinoma (laBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate. Please click here for full Prescribing Information.
Dr. Karl Lewis, Professor in the Division of Medical Oncology at the University of Colorado, discusses the evolving treatment strategy for locally advanced basal cell carcinoma (BCC) and the role of immunotherapy. This article was sponsored and developed by Regeneron in collaboration with Dr. Lewis.
How often do you see advanced BCC in your practice?
In the United States, more than two million patients are diagnosed with BCC each year and the incidence rates continue to increase over time.1,2 In most cases, BCC can be caught early and cured.2 However, in ~20,000 patients, BCC can progress to an advanced stage where the cancer becomes more difficult to treat and is potentially life-threatening.2,3
While rare, I typically see advanced BCC cases a few times each year.
Why is it important to identify early on if a patient is at risk for advanced BCC?
As with any type of cancer, detecting BCC early is critical to be able to treat the tumor.2 Fortunately, most cases of BCC remain localized and are easily amenable to local intervention, such as excision.2 However, some patients may present with what seems like an innocuous tumor but could already have spread locally under the surface of the skin. In some cases, the disease may appear in compromising places anatomically, such as on or next to the orbit or the nose, making it more difficult to remove.1,2 In these instances, we need to evaluate other forms of treatment.
When are medical oncologists like yourself usually engaged as part of a multidisciplinary team (MDT) to treat someone with advanced BCC?
In some instances, I don’t see patients with advanced BCC until after surgery has been attempted. In some cases, patients may experience disfiguration in the absence of clear margins. In other cases, patients are referred to my practice by other physicians to discuss systemic therapy options as part of their initial work-up.
Advanced BCC is best managed in a multidisciplinary setting that consists of dermatologists, Mohs or head and neck surgeons, as well as radiation and medical oncologists, who can work together to develop the best treatment plan for a particular patient.2
In my experience, the involvement of an MDT can vary based on the referring physician. For cases of advanced BCC, I encourage physicians to involve oncologists early in the treatment process, and over time, I have seen this happen more frequently.
How has the treatment landscape for locally advanced BCC evolved in recent years?
Historically, treatment options for patients with locally advanced BCC have been limited to surgery or radiotherapy.2
Some patients with locally advanced BCC may be treated with surgical procedures but determining whether locally advanced BCC is fully resectable is often a challenge.2 If tumors are not completely excised, the risk of disease recurrence is high; alternatively, wide surgical margins can lead to severe disfigurement, loss of function and other detrimental effects.2
Systemic therapies, including hedgehog pathway inhibitors (HHIs), have changed the treatment paradigm for patients with locally advanced BCC.2 However, while HHIs may be effective for many advanced cases, some patients may discontinue HHI therapy due to progressive disease or adverse events and will require another treatment.2,4
In these cases, I believe immunotherapy can play an important role. Specifically, immune checkpoint inhibitors like LIBTAYO, which targets PD-1, may be appropriate in these cases.2
Where does LIBTAYO (cemiplimab-rwlc) fit in the treatment of locally advanced BCC?
In February 2021, LIBTAYO was approved by the U.S. Food and Drug Administration (FDA) as the first treatment indicated for patients with locally advanced BCC previously treated with an HHI or for whom an HHI is not appropriate.4 The approval was based on data from the pivotal Phase 2 trial which included patients with locally advanced BCC after treatment with HHIs.5
What is the recommended dosage for LIBTAYO?
The recommended dosage of LIBTAYO is 350 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity.5
Can you elaborate on the dataset that supports the use of LIBTAYO in locally advanced BCC?
LIBTAYO was approved by the FDA based on results from the pivotal, open-label, multicenter, Phase 2, nonrandomized study that included 132 patients, of whom 84 had locally advanced BCC that had progressed on HHI therapy, were intolerant of prior HHI therapy, or had not had an objective response after nine months on HHI therapy.5 Of these 84 patients, 75% of patients discontinued HHI therapy due to disease progression/lack of response and 25% discontinued treatment due to intolerance to HHI therapy.3 Treatment continued until progression of disease, unacceptable toxicity or completion of planned treatment.5
The study excluded patients with autoimmune disease that required systemic therapy with immunosuppressant agents within five years; history of solid organ transplant; prior treatment with anti–PD-1/PD-L1 therapy or other immune checkpoint inhibitor therapy; infection with HIV, hepatitis B or hepatitis C; or Eastern Cooperative Oncology Group Performance Status ≥2.5
The 84 patients with locally advanced BCC received LIBTAYO 350 mg every three weeks as an intravenous infusion for up to 93 weeks.5 Tumor response was assessed every nine weeks for the first 45 weeks of therapy and every 12 weeks thereafter.5 The primary endpoint was confirmed objective response rate (ORR) assessed by independent central review (ICR).5 Secondary endpoints included duration of response (DOR), complete response (CR) rate and safety and tolerability.3
Among the 84 patients with locally advanced BCC, the ORR was 29% (95% CI: 19%-40%), including a 23% partial response and 6% complete response.5 The median duration of follow up was 15.1 months for patients with laBCC.5 Furthermore, the DOR had not been reached (range: 2.1-21.4+ months) and 79.2% of patients had a DOR of six months or greater.5 The median time to response was 4.2 months (range: 2.1-13.4 months).5
What was the safety profile for LIBTAYO in this pivotal trial?
The safety of LIBTAYO was evaluated in 132 patients with advanced BCC, including 84 patients with locally advanced BCC, in the Phase 2 trial.5
Serious adverse reactions (ARs) occurred in 32% of patients. Serious ARs that occurred in >1.5% (at least two patients) were urinary tract infection, colitis, acute kidney injury, adrenal insufficiency, anemia, infected neoplasm and somnolence.5 Fatal ARs occurred in 1.5% of patients who received LIBTAYO, including acute kidney injury and cachexia.5
LIBTAYO was permanently discontinued due to an AR in 13% of patients. Adverse reactions resulting in permanent discontinuation of LIBTAYO in >1.5% (at least two patients) were colitis and general physical health deterioration.5
Dosage delays of LIBTAYO due to an AR occurred in 34% of patients. ARs which required dosage delay in >2% of patients (at least three patients) included blood creatinine increased, diarrhea, colitis, fatigue, headache, pneumonitis and urinary tract infection.5
The most common ARs reported in at least 15% of patients were fatigue, musculoskeletal pain, diarrhea, rash, pruritus and upper respiratory tract infection.5 The most common Grade 3 or 4 ARs (>2%) were hypertension, colitis, fatigue, urinary tract infection, pneumonia, increased blood pressure, hypokalemia and visual impairment. The most common (>3%) laboratory abnormality worsening from baseline to Grade 3 or 4 was hyponatremia.5 The adverse reactions that occurred in ≥10% of patients receiving LIBTAYO in Study 1620 can be seen below.
Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03.
†Fatigue is a composite term that includes fatigue, asthenia, and malaise.5
‡Musculoskeletal pain is a composite term that includes arthralgia, back pain, myalgia, pain in extremity, musculoskeletal pain, neck pain, musculoskeletal stiffness, musculoskeletal chest pain, musculoskeletal discomfort, and spinal pain.5
§Rash is a composite term that includes rash maculo-papular, rash, dermatitis, dermatitis acneiform, erythema, rash pruritic, dermatitis bullous, dyshidrotic eczema, pemphigoid, rash erythematous, and urticaria.5
||Upper respiratory tract infection is a composite term that includes upper respiratory tract infection, nasopharyngitis, rhinitis, sinusitis, pharyngitis, respiratory tract infection, and viral upper respiratory tract infection.5
¶Dyspnea is a composite term that includes dyspnea and dyspnea exertional.5
#Hypertension is a composite term that includes hypertension and hypertensive crisis.5