The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda®, Merck & Co.) for patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation. The recommended dosage for this additional indication is 400 mg every six weeks (Q6W)
Cutaneous squamous cell carcinoma, a malignant proliferation of the cutaneous epithelium, traditionally represents approximately 20% of all non-melanoma skin cancers. However, with a growing elderly population and an increased focus of skin cancer screening, recent data confirmed a 1:1 ratio between basal cell carcinoma (BCC) and SCC in the Medicare fee-for-service population. And while the disease, in the majority of cases, can successfully be eradicated by surgical excision, a subset of cSCC may have a higher likelihood of recurrence, metastasis, and death. This deadly cascading threat is caused by the fact that this disease has the ability to metastasize to any organ in the body.
Metastatic cSCC, is more common in men, people over the age of 75 years of age and is diagnosed more often in people living in the south and mid-west of the United States.
This additional indication is approved under accelerated approval based on pharmacokinetic data, the relationship of exposure to efficacy, and the relationship of exposure to safety.
Continued approval is contingent upon verification and description of clinical benefit in the confirmatory trials. This new dosage option will be available in addition to the current dose of 200 mg every three weeks (Q3W).
Efficacy was investigated in KEYNOTE-629 (NCT03284424), a multicenter, multi-cohort, non-randomized, open-label trial. The trial excluded patients who had previously received therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody and those with autoimmune disease or a medical condition that required immunosuppression. Patients received pembrolizumab 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, or a maximum of 24 months. Assessment of tumor status was performed every 6 weeks during the first year and every 9 weeks during the second year.
The major efficacy outcome measures were objective response rate (ORR) and response duration as assessed by blinded independent central review according to RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The ORR was 34% (95% CI: 24, 44) and the median response duration was not reached (range: 2.7, 13.1+ months).
Undesirable adverse reactions occurring in patients with cSCC enrolled in KEYNOTE-629 were similar to those occurring in patients who received pembrolizumab as a single agent in other clinical trials. The most common adverse reactions to pembrolizumab are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.
Efficacy and safety of pembrolizumab using a dosage of 400 mg every 6 weeks for cSCC was primarily based on the modeling of dose/exposure efficacy and safety relationships and observed pharmacokinetic data in patients with melanoma.
“The important social distancing measures for COVID-19 have created a number of challenges for people with cancer, including keeping to planned treatment schedules,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.
“Today’s approval of an every six-week dosing schedule for KEYTRUDA gives doctors an option to reduce how often patients are at the clinic for their treatment,” Baynes concluded.
View full prescribing information for Pembrolizumab.
Study of Pembrolizumab (MK-3475) in Adults With Recurrent/Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) or Locally Advanced Unresectable cSCC (MK-3475-629/KEYNOTE-629) – NCT03284424
 Burton KA, Ashack KA, Khachemoune A. Cutaneous Squamous Cell Carcinoma: A Review of High-Risk and Metastatic Disease. Am J Clin Dermatol. 2016;17(5):491-508. doi:10.1007/s40257-016-0207-3
 Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA Dermatol. 2015;151(10):1081-1086. doi:10.1001/jamadermatol.2015.1187